Pharmaceutical composition comprising anti-PD-1 antibody and second antibody

Abstract

Provided is a pharmaceutical composition comprising an anti-PD-1 antibody and a second antibody, the second antibody being an anti-LAG-3 antibody. In addition, the invention also provides a preparation method of the pharmaceutical composition and application of the pharmaceutical composition in preparation of medicines for treating diseases of subjects.

Description

Pharmaceutical composition comprising an anti-PD-1 antibody and a second antibody Technical Field

[0001] The present disclosure belongs to the field of biomedicine, and specifically relates to a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof and a second antibody or an antigen-binding fragment thereof, and uses thereof. Background Art

[0002] PD-1 (Programmed death-1) is primarily expressed by activated T and B lymphocytes, and its ligands include PD-L1 and PD-L2. Binding of PD-1 to its ligand inhibits T cell activation and proliferation, downregulating the secretion of T cell immunostimulatory cytokines, thereby suppressing T cell immune responses and promoting T cell apoptosis. PD-1 is highly expressed on tumor-infiltrating lymphocytes, and its ligand is also upregulated on the surface of various tumor cells. Therefore, anti-PD-1 antibodies, by blocking the binding of PD-1 to its ligand, can interrupt the immunosuppressive signaling pathway and enhance the body's endogenous anti-tumor immune response.

[0003] Lymphocyte activation gene-3 (LAG-3) belongs to the immunoglobulin superfamily and is primarily expressed on the surface of activated T cells, NK cells, B cells, and plasmacytoid dendritic cells. LAG-3 has multiple ligands, including major histocompatibility complex class II (MHC-II), fibronectin 1 (FGL1), galectin-3, and liver sinusoidal endothelial cell lectin (LSECtin). LAG-3 negatively regulates T cells and plays a crucial role in maintaining immune homeostasis. However, multiple lines of evidence suggest that tumor cells overexpress LAG-3 ligands, which bind to LAG-3, which is highly expressed on tumor-infiltrating lymphocytes (TILs), leading to T cell dysfunction or even exhaustion, exacerbating tumor cell immune evasion and promoting tumor progression.

[0004] Anti-PD-1 antibodies can be administered in combination with anti-LAG-3 antibodies, but administration of both antibodies requires multiple doses at different time points. Therefore, a single formulation containing both antibodies would improve patient convenience and reduce drug resistance. Because each antibody has unique physical and chemical properties, such as surface-exposed residues, cleavage sites, glycation sites, deamidation sites, surface charge distribution, isoelectric point, aggregation tendency, solubility, etc., unique formulation excipients are required to maintain the stability of each antibody, making it difficult to determine a single formulation.

[0005] SUMMARY OF THE INVENTION

[0006] The present disclosure provides a pharmaceutical composition comprising an anti-PD-1 antibody or antigen-binding fragment thereof and a second antibody or antigen-binding fragment thereof. In some embodiments, the second antibody or antigen-binding fragment thereof is an anti-LAG-3 antibody or antigen-binding fragment thereof. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof and the anti-LAG-3 antibody or antigen-binding fragment thereof are present in the pharmaceutical composition at a fixed dose ratio.

[0007] In some embodiments, the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:1-15, 1:1-12, 1:1-10, 1:1-9, 1:1-8, 1:1-6, 1:1-5, 1:1-4.5, 1:1-4, 1:1-3.5, 1:1-3, 1:1-2.5, 1:1-2, 1:1-1.5, 1:1-1.25, 1:0.1-1, 1:0.4-1, or 1:0.8-1.

[0008] The present disclosure also provides a lyophilized preparation, wherein the lyophilized preparation is obtained by freeze-drying the pharmaceutical composition of the present disclosure.

[0009] The present disclosure also provides a lyophilized preparation, wherein the lyophilized preparation can form the pharmaceutical composition of the present disclosure after reconstitution.

[0010] The present disclosure also provides a medicine kit, wherein the medicine kit comprises the pharmaceutical composition of the present disclosure. The present disclosure also provides a vial, wherein the vial comprises the pharmaceutical composition of the present disclosure.

[0011] The present disclosure also provides a syringe, wherein the syringe comprises the pharmaceutical composition of the present disclosure. The present disclosure also provides an intravenous bag, wherein the intravenous bag comprises the pharmaceutical composition of the present disclosure.

[0012] The present disclosure also provides a method for preparing the pharmaceutical composition and lyophilized formulation of the present disclosure.

[0013] The present disclosure also provides a method for treating a disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition or lyophilized formulation of the present disclosure. In some embodiments, the disease comprises cancer and infectious diseases.

[0014] The present disclosure also provides a method for enhancing an immune response in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition or lyophilized formulation of the present disclosure.

[0015] Detailed Description of the Invention

[0016] Explanation of terms

[0017] In order to make the present invention more easily understood, certain technical and scientific terms are specifically defined below. Unless otherwise expressly defined herein, all other technical and scientific terms used herein have the meanings commonly understood by those skilled in the art to which the present invention belongs.

[0018] The term "buffer" refers to a pharmaceutically acceptable buffer, which refers to a substance that helps maintain the pH of a pharmaceutical composition within a desired pH range. Suitable buffers for use in the present disclosure include phosphate buffers, acetate buffers, citrate buffers, Tris buffers, or histidine buffers. In addition, mixtures of two or more buffers may also be used.

[0019] The term "phosphate buffer" refers to a buffer containing phosphate ions. Examples of phosphate buffers include sodium phosphate buffers, potassium phosphate buffers, and the like. Sodium phosphate buffers can be prepared using disodium hydrogen phosphate or a hydrate thereof (e.g., disodium hydrogen phosphate dodecahydrate) and sodium dihydrogen phosphate or a hydrate thereof (e.g., sodium dihydrogen phosphate dihydrate).

[0020] The term "acetate buffer" refers to a buffer containing acetate ions. Examples of acetate buffers include potassium acetate buffer, ammonium acetate buffer, sodium acetate buffer, and the like. Sodium acetate buffer can be prepared using acetic acid and sodium acetate or a hydrate thereof (e.g., anhydrous sodium acetate or sodium acetate trihydrate).

[0021] The term "citrate buffer" refers to a buffer containing citrate ions. Examples of citrate buffers include sodium citrate buffer, potassium citrate buffer, calcium citrate buffer, and the like. Sodium citrate buffer can be prepared using citric acid and sodium citrate or a hydrate thereof (e.g., trisodium citrate dihydrate).

[0022] The term "histidine buffer" is a buffer comprising histidine ions. Examples of histidine buffers include histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, histidine-acetate buffer, histidine-phosphate buffer, etc. Histidine-histidine hydrochloride buffer can be prepared using histidine (e.g., L-histidine) and histidine hydrochloride or a hydrate thereof (e.g., histidine hydrochloride monohydrate). Histidine-hydrochloride buffer can be prepared using histidine (e.g., L-histidine) and further adjusted to pH with hydrochloric acid. Histidine-acetate buffer can be prepared using histidine (e.g., L-histidine) and further adjusted to pH with acetic acid. Histidine-phosphate buffer can be prepared using histidine (e.g., L-histidine) and further adjusted to pH with phosphoric acid.

[0023] The term "stabilizer" refers to a substance that helps maintain the structural integrity of the active ingredient (e.g., antibody) in a pharmaceutical composition, particularly during freezing, lyophilization, storage, and / or transportation (especially when exposed to stress). In this context, a stabilizer may also function as a viscosity reducer, antioxidant, and / or isotonicity agent.

[0024] The term "antioxidant" refers to a substance that can prevent or reduce oxidation of an active ingredient (eg, an antibody) in a pharmaceutical composition.

[0025] The term "isotonic agent" refers to a substance that helps maintain the osmotic pressure of a pharmaceutical composition at or near physiological osmotic pressure.

[0026] The term "excipient" refers to any ingredient other than the active ingredient. The choice of excipient will depend, to a large extent, on factors such as the particular mode of administration, the effect of the excipient on solubility and stability, and the nature of the dosage form. As used herein, "pharmaceutically acceptable excipients" include, but are not limited to, excipients, diluents, fillers, binders, chelating agents, disintegrants, solubilizers, stabilizers, colorants, flavorings, surfactants, emulsifiers, buffers, or encapsulating materials.

[0027] The term "stable" pharmaceutical composition refers to a pharmaceutical composition in which the active ingredient (e.g., an antibody) substantially maintains its physical stability and / or chemical stability and / or biological activity when stored therein. A variety of techniques for measuring the stability and biological activity of active ingredients are available in the art, for example, as reviewed in Peptide and Protein Drug Delivery, 247-301, Vincent Lee Ed., Marcel Dekker, Inc., New York, NY, Pubs. (1991) Jones, A. Adv. Drug Delivery Rev. 10: 29-90 (1993). Stability can be measured at a selected temperature and other storage conditions for a selected time period. For example, if the active ingredient does not show a significant increase in aggregation, precipitation, and / or denaturation after visual inspection of color and / or clarity, or as measured by UV light scattering, size exclusion chromatography (SEC), and differential scanning calorimetry (DSC), then the active ingredient "retains its physical stability" in the pharmaceutical composition. An active ingredient (e.g., an antibody) "retains its chemical stability" in a pharmaceutical composition if it does not exhibit significant chemical changes. Chemical stability can be assessed by detecting and quantifying chemically altered forms of the antibody. Processes that alter the chemical structure of an antibody include hydrolysis or truncation (which can be assessed by methods such as size exclusion chromatography and SDS-PAGE), oxidation (which can be assessed by methods such as peptide mapping in combination with mass spectrometry or MALDI / TOF / MS), deamidation (which can be assessed by methods such as ion exchange chromatography, capillary isoelectric focusing, peptide mapping, isoaspartate measurement), and isomerization (which can be assessed by measuring isoaspartate content, peptide mapping, etc.). An active ingredient (e.g., an antibody) "retains its biological activity" in a pharmaceutical composition over a given period of time if its biological activity over a given period of time is within a predetermined range of the biological activity exhibited when the pharmaceutical composition was prepared, which can be determined by antigen binding assays.

[0028] "High molecular weight impurities" or "aggregates" are a general term for impurities with a molecular weight greater than that of the target active ingredient (eg, antibody).

[0029] As used herein, the term "antibody" refers to an antigen-binding protein having at least one antigen-binding domain. The antibody or fragment thereof disclosed herein may be a whole antibody or any fragment thereof, including a monoclonal antibody or fragment thereof and an antibody variant or fragment thereof. Examples of antibodies or antigen-binding fragments disclosed herein include monospecific antibodies, bispecific antibodies, multispecific antibodies, Fab fragments, Fab' fragments, F(ab)'2 fragments, Fv fragments, isolated CDR regions, single-chain Fv molecules (scFv), and other antibody fragments known in the art. Unless otherwise indicated, "antibodies or antigen-binding fragments thereof" disclosed herein include whole antibodies and any antigen-binding fragments thereof or single chains. Conventional "whole antibodies" are glycoproteins comprising two heavy (H) chains and two light (L) chains, the heavy and light chains being linked by disulfide bonds. Each heavy chain consists of a heavy chain variable region (VH) and a heavy chain constant region (CH). The heavy chain constant region consists of three domains, namely CH1, CH2, and CH3. Each light chain consists of a light chain variable region (VL) and a light chain constant region (CL). The light chain constant region is composed of a domain, CL. The VH and VL regions can also be divided into hypervariable regions, i.e., complementary determining regions (CDRs), and framework regions (FRs) whose sequences are relatively conserved. Each VH and VL is composed of three CDRs and four FRs, respectively, from the amino terminus to the carboxyl terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable region of an antibody comprises a binding domain that interacts with an antigen. The constant region of an antibody can mediate the binding of an immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. At the same time, as will be appreciated by those skilled in the art, special "whole antibodies," such as nanobodies, have only heavy (H) chains and no light (L) chains.

[0030] An "antigen-binding fragment" of an antibody refers to one or more fragments of an antibody that retain the function of specifically binding to an antigen. It has been demonstrated that the antigen-binding function of an antibody can be implemented by fragments of the entire antibody. Examples encompassed within the "antigen-binding fragment" of an antibody include: (i) a Fab fragment: a monovalent fragment consisting of a VL, VH, CL, and CH1 domains; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments connected by a disulfide bridge in the hinge region; (iii) an Fd fragment consisting of a VH and CH1 domain; (iv) an Fv fragment consisting of the VL and VH domains of a single antibody arm; (v) a dAb fragment consisting of a VH domain (see Ward et al., Nature. 341: 544-546 (1989)); (vi) an isolated complementary determining region (CDR); and (vii) a nanobody, a heavy chain variable region comprising a single variable domain and two constant domains. In addition, although the two domains VL and VH of the Fv fragment are encoded by different genes, VH and VL can be connected into a single protein chain by a recombinant method through a synthetic linker, wherein VL and VH pair to form a monovalent molecule (called single-chain Fv (scFv); see, for example, Bird et al., Science. 242: 423-426 (1988); Huston et al., Proc. Natl. Acad. Sci. 85: 5879-5883 (1988)). These single-chain antibodies are also encompassed by the term antigen-binding fragment. In addition, recombinant polypeptides, fusion proteins, and immunoconjugates comprising the antigen-binding fragment are also encompassed by the term antigen-binding fragment.

[0031] A "chimeric antibody" is an antibody having at least a portion of a heavy chain variable region and at least a portion of a light chain variable region derived from one species, and at least a portion of a constant region derived from another species. For example, in one embodiment, a chimeric antibody may comprise a murine variable region and a human constant region.

[0032] A "humanized antibody" is an antibody that contains complementarity determining regions (CDRs) derived from a non-human antibody and framework and constant regions derived from a human antibody. For example, an anti-LAG-3 antibody and an anti-PD-1 antibody can contain CDRs derived from one or more murine antibodies and human framework and constant regions. Additional anti-LAG-3 antibodies or variants thereof comprising the HCDRs and LCDRs provided herein can be generated using any human framework sequences and are also encompassed by the present disclosure. Additional anti-PD-1 antibodies or variants thereof comprising the HCDRs and LCDRs provided herein can be generated using any human framework sequences and are also encompassed by the present disclosure.

[0033] The term "identity" is also known as consistency. The "percentage (%) identity" of an amino acid sequence refers to the percentage of amino acid residues in the sequence to be aligned that are identical to the amino acid residues in the specific amino acid sequence shown in this article, after comparing the sequence to be aligned and, if necessary, introducing gaps to achieve maximum sequence identity, and not considering any conservative substitutions as part of sequence identity. The alignment of amino acid sequences for identity can be performed in a variety of ways within the scope of the art, such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine the appropriate parameters for aligning sequences, including any algorithm needed to obtain maximum alignment over the full length of the comparison sequence.

[0034] The term "fixed dose ratio" refers to that two or more different antibodies or antigen-binding fragments thereof in a single pharmaceutical composition are present in a specific (fixed) ratio relative to each other in the pharmaceutical composition, and the ratio is the fixed dose ratio. In some embodiments, the fixed dose ratio is based on the mass (e.g., mg) of the antibody or antigen-binding fragment thereof. In certain embodiments, the fixed dose ratio is based on the concentration (e.g., mg / mL) of the antibody or antigen-binding fragment thereof.

[0035] Herein, "multiples / fractions" refer to multiples or fractions of a parameter / value. For example, multiples of 200 mg include 400 mg (2 times), 600 mg (3 times), 800 mg (4 times), and 1000 mg (5 times); fractions of 200 mg include 20 mg (1 / 10), 25 mg (1 / 8), 40 mg (1 / 5), 50 mg (1 / 4), and 100 mg (1 / 2).

[0036] The term "treatment" generally refers to an operation to obtain a desired pharmacological and / or physiological effect. The effect can be preventive, in terms of completely or partially preventing a disease or its symptoms; and / or therapeutic, in terms of partially or completely stabilizing or curing a disease and / or side effects produced by the disease. As used herein, "treatment" encompasses any treatment of a patient's disease, including but not limited to preventing the occurrence or recurrence of the disease, alleviating the symptoms of the disease, reducing any direct or indirect pathological consequences of the disease, preventing the metastasis of the disease, slowing the progression of the disease, improving or alleviating the state of the disease, prolonging the frequency and duration of symptom-free periods, and resolving or improving the prognosis of the disease.

[0037] "Therapeutically effective amount" or "therapeutically effective dose" refers to any amount of a drug that protects a subject from the onset of disease or promotes disease regression, which can be demonstrated by a reduction in the severity of disease symptoms, an increase in the frequency and duration of disease symptom-free periods, or the prevention of impairment or disability resulting from disease affliction. The ability of a therapeutic agent to promote disease regression can be evaluated using a variety of methods known to skilled practitioners, such as in human subjects during clinical trials, in animal model systems predictive of efficacy in humans, or by measuring the activity of the agent in in vitro assays.

[0038]

[00146] The terms "administering" or "administering" refer to the physical introduction of a therapeutic agent into a subject using any of a variety of methods and delivery systems known to those skilled in the art.

[0039] As used herein, the terms "subject," "patient," or "subject" are used interchangeably. "Subject," "patient," or "subject" includes any human or non-human animal. The term "non-human animal" includes, but is not limited to, vertebrates such as non-human primates, sheep, dogs, and rodents (e.g., mice, rats, and guinea pigs). In some embodiments, the subject, patient, or subject is a mammal. In some embodiments, the subject, patient, or subject is a mouse. In some embodiments, the subject, patient, or subject is a human.

[0040] The articles "a" and "an" are used herein to refer to one or more than one (i.e., at least one) of the grammatical object of the article. For example, "a pharmaceutical composition" refers to one pharmaceutical composition or more than one pharmaceutical composition.

[0041] As used herein, "about" means within the acceptable error range for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, i.e., on the limitations of the measurement system. For example, "about" can mean within one or more standard deviations, as practiced in the art. Alternatively, "about" can mean a range of up to ±5%, for example, within ±2%, ±1%, or ±0.5% of the range of a given specific value. When specific values ​​or parameters are given herein or in the claims, they are assumed to be modified by "about" unless otherwise indicated.

[0042] As used herein, unless the context dictates otherwise, the words "comprising," "including," and "containing" will be understood to mean including the recited step or element or group of steps or elements but not excluding any other step or element or group of steps or elements. "Consisting of" means including and limited to what follows the phrase "consisting of." Thus, the phrase "consisting of" means that the listed elements are required or essential, and no other elements may be present. "Consisting essentially of" means including any element listed after the phrase and is limited to other elements that do not interfere with or contribute to the activity or action of the listed elements. Thus, the phrase "consisting essentially of" means that the listed elements are required or essential, but other elements are optional and may be present or absent depending on whether they affect the activity or action of the listed elements.

[0043] As described herein, any numerical range (e.g., a concentration range, a percentage range, or a ratio range) should be understood to include any integer value within the range, and where appropriate, fractions thereof (such as tenths and hundredths of integers), unless otherwise indicated.

[0044] Pharmaceutical composition

[0045] The present disclosure provides a pharmaceutical composition, wherein the pharmaceutical composition comprises an anti-PD-1 antibody or an antigen-binding fragment thereof and a second antibody or an antigen-binding fragment thereof. In some embodiments, the second antibody or an antigen-binding fragment thereof is an anti-LAG-3 antibody or an antigen-binding fragment thereof.

[0046] As used herein, a "pharmaceutical composition" includes two or more antibodies or antigen-binding fragments thereof, wherein the two or more antibodies or antigen-binding fragments thereof are formulated together and stored as a combination product in a single vial or container (e.g., an injection device), rather than being formulated and stored separately and then mixed before administration or administered separately. The purpose of a pharmaceutical composition is to make the active ingredients (e.g., two or more antibodies or antigen-binding fragments thereof) suitable for manufacture and / or administration to a patient and to maintain biological activity and / or stability during storage and subsequent use.

[0047] In some embodiments, the pharmaceutical composition of the present disclosure is an injection. In some embodiments, the injection includes but is not limited to a non-lyophilized water-soluble preparation or a water-soluble preparation reconstituted from a lyophilized preparation.

[0048] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof and the anti-LAG-3 antibody or antigen-binding fragment thereof are present in the pharmaceutical composition at a fixed dose ratio. In some embodiments, the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof in the pharmaceutical composition is 1:1-15, 1:1-12, 1:1-10, 1:1-9, 1:1-8, 1:1-6, 1:1-5, 1:1-4.5, 1:1-4, 1:1-3.5, 1:1-3, 1:1-2.5, 1:1-2, 1:1-1.5, 1:1-1.25, 1:0.1-1, 1:0.4-1, or 1:0.8-1. In some embodiments, the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof in the pharmaceutical composition is 1:1-3. In some embodiments, the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof in the pharmaceutical composition is 15:1, 12:1, 10:1, 9:1, 8:1, 6:1, 5:1, 4.5:1, 4:1, 3.5:1, 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1, 1:1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:6, 1:8, 1:9, 1:10, 1:12, or 1:15. In some embodiments, the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof in the pharmaceutical composition is 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1, 1:1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, or 1:6. In some embodiments, the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof in the pharmaceutical composition is 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4. In some embodiments, the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof in the pharmaceutical composition is 1:1.5, 1:2, or 1:3. In some embodiments, the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof in the pharmaceutical composition is 1:3.

[0049] In some embodiments, the fixed dose ratio is the mass ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof in the pharmaceutical composition.

[0050] In some embodiments, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100-200 mg, or any multiple / fraction thereof, such as 100 mg or 200 mg, or a multiple / fraction thereof. In some embodiments, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg. In some embodiments, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg.

[0051] In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof has a mass of 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or any multiple / fraction thereof, such as 40 mg, 80 mg, 120 mg, 160 mg, 200 mg, 240 mg, 280 mg, 300 mg, 320 mg. In some embodiments, the weight of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In some embodiments, the weight of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg.

[0052] In some embodiments, the pharmaceutical composition comprises 100-200 mg, or any multiple / fraction thereof, of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or any multiple / fraction thereof, of an anti-LAG-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 100 mg, or 200 mg, or multiples thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 40 mg, 80 mg, 120 mg, 160 mg, 200 mg, 240 mg, 280 mg, 300 mg, 320 mg, 360 mg, 400 mg, 440 mg, 480 mg, 500 mg, 520 mg, 560 mg, 600 mg, 640 mg, 680 mg, 700 mg, 740 mg, 780 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, or 1800 mg, or multiples thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 100 mg, 200 mg, or multiples thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 200 mg, or multiples thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 200 mg, or multiples thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 300 mg, 400 mg, or 600 mg, or multiples thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or multiples / fractions thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples / fractions thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or 200 mg of an anti-PD-1 antibody or antigen-binding fragment thereof, and 300 mg or 600 mg of an anti-LAG-3 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 200 mg of an anti-PD-1 antibody or antigen-binding fragment thereof, and 600 mg of an anti-LAG-3 antibody or antigen-binding fragment thereof.In some embodiments, the pharmaceutical composition comprises 100 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 300 mg of an anti-LAG-3 antibody or an antigen-binding fragment thereof.

[0053] In some embodiments, the fixed dose ratio is the concentration ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof in the pharmaceutical composition.

[0054] In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 1-100 mg / mL, 1-80 mg / mL, 2-60 mg / mL, 3-30 mg / mL, 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof includes, but is not limited to, 1 mg / mL, 2 mg / mL, 3 mg / mL, 4 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, 11 mg / mL, 12 mg / mL, 13 mg / mL, 14 mg / mL, 15 mg / mL, 20 mg / mL, 21 mg / mL, 22 mg / mL, 23 mg / mL, 24 mg / mL, 25 mg / mL, 30 mg / mL, 40 mg / mL, 50 mg / mL, 60 mg / mL, 70 mg / mL, or 80 mg / mL, or any range thereof. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4 mg / mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 8 mg / mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 10 mg / mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 15 mg / mL.

[0055] In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof is at a concentration of 1-200 mg / mL, 2-160 mg / mL, 3-120 mg / mL, 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In some embodiments, the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof includes, but is not limited to, 3 mg / mL, 4 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 7.5 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, 12 mg / mL, 14 mg / mL, 15 mg / mL, 16 mg / mL, 18 mg / mL, 20 mg / mL, 22 mg / mL, 22.5 mg / mL, 24 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 55 mg / mL, 60 mg / mL, 65 mg / mL, 70 mg / mL, 75 mg / mL, 80 mg / mL, 90 mg / mL, 100 mg / mL, or 120 mg / mL, or any range thereof. In some embodiments, the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 6 mg / mL. In some embodiments, the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 7.5 mg / mL. In some embodiments, the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 8 mg / mL. In some embodiments, the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 10 mg / mL. In some embodiments, the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 12 mg / mL. In some embodiments, the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In some embodiments, the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 16 mg / mL. In some embodiments, the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 20 mg / mL. In some embodiments, the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 24 mg / mL. In some embodiments, the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 30 mg / mL.

[0056] In some embodiments, the pharmaceutical composition comprises 1-100 mg / mL, 1-80 mg / mL, 2-60 mg / mL, 3-30 mg / mL, 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 1-200 mg / mL, 2-160 mg / mL, 3-120 mg / mL, 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL of an anti-LAG-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL of an anti-LAG-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 1 mg / mL, 2 mg / mL, 3 mg / mL, 4 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, 11 mg / mL, 12 mg / mL, 13 mg / mL, 14 mg / mL, 15 mg / mL, 20 mg / mL, 21 mg / mL, 22 mg / mL, 23 mg / mL, 24 mg / mL, 25 mg / mL, 30 mg / mL, 40 mg / mL, 50 mg / mL, 60 mg / mL, 70 mg / mL, or 80 mg / mL of an anti-PD-1 antibody or antigen-binding fragment thereof, and 3 mg / mL, 4 mg / mL, 5 mg / mL, 6 mg / mL, 70 mg / mL, or 80 mg / mL of an anti-PD-1 antibody or antigen-binding fragment thereof. In some embodiments, the present invention provides an anti-LAG-3 antibody or antigen-binding fragment thereof at a dosage of 1 mg / mL, 6 mg / mL, 7 mg / mL, 7.5 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, 12 mg / mL, 14 mg / mL, 15 mg / mL, 16 mg / mL, 18 mg / mL, 20 mg / mL, 22 mg / mL, 22.5 mg / mL, 24 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 55 mg / mL, 60 mg / mL, 65 mg / mL, 70 mg / mL, 75 mg / mL, 80 mg / mL, 90 mg / mL, 100 mg / mL, or 120 mg / mL of an anti-LAG-3 antibody or antigen-binding fragment thereof.In some embodiments, the pharmaceutical composition comprises 4 mg / mL, 5 mg / mL, 8 mg / mL, 10 mg / mL, 12 mg / mL, or 15 mg / mL of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 4 mg / mL, 6 mg / mL, 7.5 mg / mL, 8 mg / mL, 10 mg / mL, 12 mg / mL, 15 mg / mL, 16 mg / mL, 20 mg / mL, 24 mg / mL, or 30 mg / mL of an anti-LAG-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 4 mg / mL or 5 mg / mL of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 7.5 mg / mL, 8 mg / mL, 10 mg / mL, 12 mg / mL, or 15 mg / mL of an anti-LAG-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 12 mg / mL of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 4 mg / mL of an anti-LAG-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 5 mg / mL of an anti-PD-1 antibody or an antigen-binding fragment thereof and 7.5 mg / mL of an anti-LAG-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 5 mg / mL of an anti-PD-1 antibody or an antigen-binding fragment thereof and 15 mg / mL of an anti-LAG-3 antibody or an antigen-binding fragment thereof.

[0057] The pharmaceutical compositions of the present disclosure may further comprise one or more pharmaceutically acceptable excipients, such as buffers, stabilizers, diluents, chelating agents, and surfactants.

[0058] The pharmaceutical composition of the present disclosure further comprises one or more buffers. In some embodiments, the buffer comprises a histidine buffer, an acetate buffer, a Tris buffer, a phosphate buffer, or a citrate buffer. In some embodiments, the buffer comprises a histidine buffer or an acetate buffer. In some embodiments, the buffer comprises a histidine buffer. In some embodiments, the buffer comprises an acetate buffer.

[0059] In some embodiments, the histidine buffer can be a histidine-histidine hydrochloride buffer, a histidine-hydrochloric acid buffer, a histidine-acetate buffer, or a histidine-phosphate buffer. In some embodiments, the histidine buffer can be a histidine-acetate buffer. In some embodiments, the acetate buffer can be a sodium acetate buffer, a potassium acetate buffer, or an ammonium acetate buffer. In some embodiments, the acetate buffer can be a sodium acetate buffer. In some embodiments, the phosphate buffer can be a sodium phosphate buffer or a potassium phosphate buffer. In some embodiments, the citrate buffer can be a sodium citrate buffer, a potassium citrate buffer, or a calcium citrate buffer.

[0060] In some embodiments, the concentration of the buffer is 1-100 mM, 2-80 mM, 5-60 mM, 10-40 mM, or 10-20 mM. In some embodiments, the concentration of the buffer includes but is not limited to: 5 mM, 10 mM, 11 mM, 12 mM, 13 mM, 14 mM, 15 mM, 16 mM, 17 mM, 18 mM, 19 mM, 20 mM, 21 mM, 22 mM, 23 mM, 24 mM, 25 mM, 26 mM, 27 mM, 28 mM, 29 mM, 30 mM, 32 mM, 34 mM, 36 mM, 38 mM, 40 mM, 50 mM, or 60 mM, or a range formed by any value. In some embodiments, the concentration of the buffer is 10 mM. In some embodiments, the concentration of the buffer is 20 mM. In some embodiments, the buffer comprises a histidine buffer or an acetate buffer. In some embodiments, the buffer comprises a histidine-acetate buffer or a sodium acetate buffer. In some embodiments, the buffer comprises a histidine buffer. In some embodiments, the buffer comprises a histidine-acetate buffer.

[0061] In some embodiments, the pH of the buffer is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In some embodiments, the pH of the buffer includes, but is not limited to, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, or 7, or a range formed by any value. In some embodiments, the pH of the buffer is 5. In some embodiments, the pH of the buffer is 5.3. In some embodiments, the pH of the buffer is 5.5. In some embodiments, the pH of the buffer is 5.8. In some embodiments, the pH of the buffer is 6. In some embodiments, the pH of the buffer is 6.2. In some embodiments, the pH of the buffer is 6.3. In some embodiments, the pH of the buffer is 6.5.

[0062] The pharmaceutical composition of the present disclosure also includes one or more stabilizers. In some embodiments, the stabilizer is selected from sugar alcohol (for example, mannitol, sorbitol), disaccharides (for example, trehalose, sucrose, maltose, lactose), monosaccharides (for example, dextrose (D-glucose)), amino acids (for example, lysine, glycine, proline, arginine or its pharmaceutically acceptable salt) or salt (for example, sodium chloride). In some embodiments, the stabilizer is selected from mannitol, sorbitol, trehalose, sucrose, maltose, lactose, lysine, glycine, proline, arginine or its pharmaceutically acceptable salt or sodium chloride. In some embodiments, the stabilizer is selected from mannitol, sorbitol, trehalose, sucrose, proline, arginine or its pharmaceutically acceptable salt or sodium chloride. In some embodiments, the stabilizer is selected from sucrose, proline, arginine or its pharmaceutically acceptable salt.

[0063] In some embodiments, the pharmaceutical composition comprises mannitol, sorbitol, trehalose, sucrose, maltose, lactose, lysine, glycine, proline, arginine or a pharmaceutically acceptable salt thereof, and / or sodium chloride. In some embodiments, the pharmaceutical composition comprises mannitol, sorbitol, trehalose, sucrose, proline, arginine or a pharmaceutically acceptable salt thereof, and / or sodium chloride. In some embodiments, the pharmaceutical composition comprises sucrose, proline, and / or arginine or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises sucrose. In some embodiments, the pharmaceutical composition comprises sucrose and proline. In some embodiments, the pharmaceutical composition comprises sucrose and arginine or a pharmaceutically acceptable salt thereof.

[0064] In some embodiments, the concentration of the stabilizer is 1-400 mg / mL, 10-300 mg / mL, 20-200 mg / mL, 40-200 mg / mL, 40-180 mg / mL, 60-180 mg / mL, or 70-170 mg / mL. In some embodiments, the concentration of the stabilizer includes but is not limited to: 10 mg / mL, 20 mg / mL, 24 mg / mL, 30 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 54 mg / mL, 60 mg / mL, 65 mg / mL, 70 mg / mL, 80 mg / mL, 85 mg / mL, 89 mg / mL, 90 mg / mL, 100 mg / mL, 110 mg / mL, 113 mg / mL, 120 mg / mL, 130 mg / mL, 140 mg / mL, 150 mg / mL, 1

[0014] In some embodiments, the present invention provides an intravenous initiation dose of at least 54 mg / mL, 160 mg / mL, 164 mg / mL, 170 mg / mL, 178 mg / mL, 180 mg / mL, 190 mg / mL, 200 mg / mL, 202 mg / mL, 210 mg / mL, 220 mg / mL, 230 mg / mL, 240 mg / mL, 243 mg / mL, 250 mg / mL, 260 mg / mL, 267 mg / mL, 270 mg / mL, 280 mg / mL, 290 mg / mL, 291 mg / mL, or 300 mg / mL, or a range formed by any value.In some embodiments, the concentration of the stabilizer includes but is not limited to: 10.3 mg / mL, 13.7 mg / mL, 17.1 mg / mL, 20.5 mg / mL, 27.4 mg / mL, 30.8 mg / mL, 34.2 mg / mL, 34.5 mg / mL, 37.7 mg / mL, 41.1 mg / mL, 44.5 mg / mL, 47.9 mg / mL, 51.3 mg / mL, 54.8 mg / mL, 58.2 mg / mL, 61.6 mg / mL, 68.5 mg / mL, 71.9 mg / mL, 75.3 mg / mL, 78.7 mg / mL, 82.2 mg / mL, 85.6 mg / mL, 92.4 mg / mL, 95.8 mg / mL, 99.3 mg / mL, 102.7 mg / mL g / mL, 106.1mg / mL, 108.1mg / mL, 109.5mg / mL, 116.4mg / mL, 119.8mg / mL, 123.2mg / mL, 126.7mg / mL, 130.1mg / mL, 133.5mg / mL, 136.9mg / mL, 140.3mg / mL, 143.8mg / mL, 147 .2mg / mL, 150.6mg / mL, 157.5mg / mL, 160.9mg / mL, 164.3mg / mL, 167.7mg / mL, 171.2mg / mL, 174.6mg / mL, 181.4mg / mL, 184.8mg / mL, 188.3mg / mL, 191.7mg / mL, 195.1mg / mL, 198.5mg / mL, 205.4mg / mL, 208.8mg / mL, 212.2mg / mL, 215.6mg / mL, 219.1mg / mL, 222.5mg / mL, 225.9 mg / mL, 229.3mg / mL, 232.8mg / mL, 236.2mg / mL, 239.6mg / mL, 246.5mg / mL, 249.9mg / mL, 253.3mg / mL, In some embodiments, the concentration of the stabilizer is 256.7 mg / mL, 260.1 mg / mL, 263.6 mg / mL, 270.4 mg / mL, 273.8 mg / mL, 277.3 mg / mL, 280.7 mg / mL, 284.1 mg / mL, 287.5 mg / mL, 294.4 mg / mL, 297.8 mg / mL, 301.2 mg / mL, 304.6 mg / mL, or 308.1 mg / mL, or a range formed by any value. In some embodiments, the concentration of the stabilizer is 80-164.3 mg / mL. In some embodiments, the concentration of the stabilizer is 50 mg / mL. In some embodiments, the concentration of the stabilizer is 80 mg / mL. In some embodiments, the concentration of the stabilizer is 85 mg / mL.In some embodiments, the concentration of the stabilizer is 85.6 mg / mL. In some embodiments, the concentration of the stabilizer is 100 mg / mL. In some embodiments, the concentration of the stabilizer is 108.1 mg / mL. In some embodiments, the concentration of the stabilizer is 164 mg / mL. In some embodiments, the concentration of the stabilizer is 164.3 mg / mL. In some embodiments, the concentration of the stabilizer is 200-500 mM, 230-480 mM, 250-350 mM, or 310-320 mM. In some embodiments, the concentration of the stabilizer is 315.8 mM. In some embodiments, the concentration of the stabilizer is 316 mM. In some embodiments, the stabilizer is selected from sucrose, proline, arginine, or a pharmaceutically acceptable salt thereof. In some embodiments, the stabilizer is selected from sucrose.

[0065] In some embodiments, the concentration of the stabilizer is 10-1000 mM, 50-800 mM, 100-700 mM, 100-600 mM, 150-600 mM, 200-600 mM, or 200-500 mM. In some embodiments, the concentration of the stabilizer includes but is not limited to: 50mM, 60mM, 80mM, 100mM, 110mM, 120mM, 130mM, 140mM, 146mM, 150mM, 160mM, 170mM, 180mM, 190mM, 200mM, 210mM, 220mM, 230mM, 233mM, 240mM, 250mM, 260mM, 270mM, 280mM, 290mM, 300mM, 310mM, 320mM, 330mM, 340mM, 350mM, 360mM, 370mM, 380mM, 390mM, 400mM, 410mM, 420mM, 430mM, 440mM, 450mM, 460mM, 470mM, 480mM, 490mM, 500mM, 510mM, 520mM, 530mM, 540mM, 550mM, 560mM, 570mM, 580mM, 590mM, 600mM, 610mM, 620mM, 630mM, 640mM, 650mM, 660mM, 670mM, 680mM, 690mM, 700mM, 710mM, 720mM, 730mM, 740mM, 750mM, 70mM, 780mM, 790mM, or 800mM, or a range formed by any value. In some embodiments, the concentration of the stabilizer is 200-300 mM. In some embodiments, the concentration of the stabilizer is 146 mM. In some embodiments, the concentration of the stabilizer is 200 mM. In some embodiments, the concentration of the stabilizer is 233 mM. In some embodiments, the concentration of the stabilizer is 250 mM. In some embodiments, the concentration of the stabilizer is 300 mM. In some embodiments, the concentration of the stabilizer is 400 mM. In some embodiments, the concentration of the stabilizer is 480 mM. In some embodiments, the concentration of the stabilizer is 500 mM. In some embodiments, the stabilizer is selected from sucrose, proline, arginine, or a pharmaceutically acceptable salt thereof. In some embodiments, the stabilizer is selected from proline.

[0066] Pharmaceutical composition of the present disclosure also includes one or more surfactants. In some embodiments, the surfactant is a nonionic surfactant. In some embodiments, the surfactant includes polysorbate (for example, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, polysorbate 81, polysorbate 85), poloxamer (for example, poloxamer 181, poloxamer 188, poloxamer 407) or polyethylene glycol etc. In some embodiments, the surfactant includes polysorbate (for example, polysorbate 80 or polysorbate 20). In some embodiments, the surfactant includes polysorbate 80.

[0067] In some embodiments, the concentration of the surfactant is 0.01-3 mg / mL, 0.04-2 mg / mL, 0.08-1.6 mg / mL, 0.1-1.2 mg / mL, 0.1-1 mg / mL, 0.2-0.8 mg / mL, or 0.4-0.8 mg / mL. In some embodiments, the concentration of the surfactant includes but is not limited to: 0.01 mg / mL, 0.04 mg / mL, 0.06 mg / mL, 0.08 mg / mL, 0.1 mg / mL, 0.15 mg / mL, 0.2 mg / mL, 0.3 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, 0.7 mg / mL, 0.8 mg / mL, 0.9 mg / mL, 1 mg / mL, 1.1 mg / mL, 1.2 mg / mL, 1.3 mg / mL, 1.4 mg / mL, 1.5 mg / mL, 1.6 mg / mL, or 2 mg / mL, or a range formed by any value. In some embodiments, the concentration of the surfactant is 0.2 mg / mL. In some embodiments, the concentration of the surfactant is 0.4 mg / mL. In some embodiments, the concentration of the surfactant is 0.5 mg / mL. In some embodiments, the concentration of the surfactant is 0.6 mg / mL. In some embodiments, the concentration of the surfactant is 0.8 mg / mL.In some embodiments, the surfactant comprises polysorbate 80 or polysorbate 20.

[0068] In some embodiments, the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In some embodiments, the pH of the pharmaceutical composition includes, but is not limited to, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, or 7, or any range thereof. In some embodiments, the pH of the pharmaceutical composition is 5. In some embodiments, the pH of the pharmaceutical composition is 5.3. In some embodiments, the pH of the pharmaceutical composition is 5.5. In some embodiments, the pH of the pharmaceutical composition is 5.8. In some embodiments, the pH of the pharmaceutical composition is 6. In some embodiments, the pH of the pharmaceutical composition is 6.2. In some embodiments, the pH of the pharmaceutical composition is 6.3. In some embodiments, the pH of the pharmaceutical composition is 6.5.

[0069] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) a buffer, (c) one or more stabilizers, and (d) a surfactant; wherein the fixed dose ratio of the anti-PD-1 antibody or an antigen-binding fragment thereof to the anti-LAG-3 antibody or an antigen-binding fragment thereof is 1:1-9, 1:1-8, 1:1-6, 1:1-5, 1:1-4.5, 1:1-4, 1:1-3.5, 1:1- 1, 1:1-2.5, 1:1-2, 1:1-1.5, 1:1-1.25, 1:0.1-1, 1:0.4-1, or 1:0.8-1 (e.g., 9:1, 8:1, 6:1, 5:1, 4.5:1, 4:1, 3.5:1, 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1, 1:1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:6, 1:8, 1:9). In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) a buffer, (c) one or more stabilizers, and (d) a surfactant; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1, 1:1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, or 1:6 (e.g., 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4). In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) a buffer, (c) one or more stabilizers, and (d) a surfactant; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4.In such specific embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 1-100 mg / mL, 1-80 mg / mL, 2-60 mg / mL, 3-30 mg / mL, 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 1-200 mg / mL, 2-160 mg / mL, 3-120 mg / mL, 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100-200 mg, or any multiple / fraction thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or any multiple / fraction thereof. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, or a multiple / fraction thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or any multiple / fraction thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples / fractions thereof.In some embodiments, the pharmaceutical composition comprises 100 mg or multiples / fractions thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples / fractions thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg.

[0070] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., acetate buffer or histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or pharmaceutically acceptable salts thereof, and / or sodium chloride), and (d) 0.01-3 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment is 1:1-9, 1:1-8, 1:1-6, 1:1-5, 1:1-6, 1:1-7, 1:1-8, 1:1-9, 1:1-10, 1:1-11, 1:1-12, 1:1-13, 1:1-14, 1:1-15, 1:1-16, 1:1-17, 1:1-18, 1:1-19, 1:1-20, 1:1-21, 1:1-22, 1:1-23, 1:1-24, 1:1-25 :1-4.5, 1:1-4, 1:1-3.5, 1:1-3, 1:1-2.5, 1:1-2, 1:1-1.5, 1:1-1.25, 1:0.1-1, 1:0.4-1 or 1:0.8-1 (e.g., 9:1, 8:1, 6:1, 5:1, 4.5:1, 4:1, 3.5:1, 3:1, 2.5:1, 2 :1, 1.5:1, 1.25:1, 1:1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:6, 1:8, 1:9), and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., acetate buffer or histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or a pharmaceutically acceptable salt thereof, and / or sodium chloride), and (d) 0.01-3 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the anti-PD-1 antibody or its antigen-binding fragment and the anti-LAG-3 antibody or its antigen-binding fragment are combined. The fixed dose ratio of the AG-3 antibody or antigen-binding fragment thereof is 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1, 1:1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, or 1:6 (e.g., 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4), and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., sodium acetate buffer, histidine buffer, or histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and / or arginine or pharmaceutically acceptable salts thereof), and (d) 0.01-3 mg / mL surfactant (e.g., polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In such specific embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 1-100 mg / mL, 1-80 mg / mL, 2-60 mg / mL, 3-30 mg / mL, 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 1-200 mg / mL, 2-160 mg / mL, 3-120 mg / mL, 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL.In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100-200 mg, or any multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or any multiples / fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, or a multiples / fraction thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or any multiples / fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or multiples thereof of the anti-PD-1 antibody or antigen-binding fragment thereof and 200 mg, 300 mg, or 400 mg, or multiples thereof of the anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or the antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or the antigen-binding fragment thereof is 300 mg.

[0071] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 2-80 mM buffer (e.g., acetate buffer or histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or pharmaceutically acceptable salts thereof, and / or sodium chloride), and (d) 0.04-2 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:1-9, 1:1-8, 1:1-6, 1:1-5, 1:1-4.5, 1:1-4, 1:1-3.5, 1:1-3, 1:1-2.5, 1:1-2, 1:1-1.5, 1:1-1.25, 1:0.1-1, 1:0.4-1, or 1:0.8-1 (e.g., 9:1, 8:1, 6:1, 5:1, 4.5:1, 4:1, 3.5:1, 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1, 1:1 , 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:6, 1:8, 1:9), and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 2-80 mM buffer (e.g., acetate buffer or histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or a pharmaceutically acceptable salt thereof, and / or sodium chloride), and (d) 0.04-2 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the anti-PD-1 antibody or its antigen-binding fragment and the anti-LAG-3 antibody or its antigen-binding fragment are combined. The fixed dose ratio of the AG-3 antibody or antigen-binding fragment thereof is 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1, 1:1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, or 1:6 (e.g., 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4), and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 2-80 mM buffer (e.g., sodium acetate buffer, histidine buffer, or histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and / or arginine or pharmaceutically acceptable salts thereof), and (d) 0.04-2 mg / mL surfactant (e.g., polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In such specific embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 1-100 mg / mL, 1-80 mg / mL, 2-60 mg / mL, 3-30 mg / mL, 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 1-200 mg / mL, 2-160 mg / mL, 3-120 mg / mL, 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL.In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100-200 mg, or any multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or any multiples / fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, or a multiples / fraction thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or any multiples / fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or multiples thereof of the anti-PD-1 antibody or antigen-binding fragment thereof and 200 mg, 300 mg, or 400 mg, or multiples thereof of the anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or the antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or the antigen-binding fragment thereof is 300 mg.

[0072] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 5-60 mM buffer (e.g., acetate buffer or histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or pharmaceutically acceptable salts thereof, and / or sodium chloride), and (d) 0.08-1.6 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:1-9, 1:1-8, 1:1-6, 1:1-5, 1:1-4.5, or 1:1-4. , 1:1-3.5, 1:1-3, 1:1-2.5, 1:1-2, 1:1-1.5, 1:1-1.25, 1:0.1-1, 1:0.4-1 or 1:0.8-1 (e.g., 9:1, 8:1, 6:1, 5:1, 4.5:1, 4:1, 3.5:1, 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1, 1:0.1-1, 1:0.4-1 or 1:0.8-1 1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:6, 1:8, 1:9), and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 5-60 mM buffer (e.g., acetate buffer or histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or a pharmaceutically acceptable salt thereof, and / or sodium chloride), and (d) 0.08-1.6 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the anti-PD-1 antibody or its antigen-binding fragment and the anti-LAG-3 antibody or its antigen-binding fragment are combined. The fixed dose ratio of the LAG-3 antibody or antigen-binding fragment thereof is 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1, 1:1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, or 1:6 (e.g., 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4), and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 5-60 mM buffer (e.g., sodium acetate buffer, histidine buffer, or histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and / or arginine or pharmaceutically acceptable salts thereof), and (d) 0.08-1.6 mg / mL surfactant (e.g., polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In such specific embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 1-100 mg / mL, 1-80 mg / mL, 2-60 mg / mL, 3-30 mg / mL, 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 1-200 mg / mL, 2-160 mg / mL, 3-120 mg / mL, 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL.In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100-200 mg, or any multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or any multiples / fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, or a multiples / fraction thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or any multiples / fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or multiples thereof of the anti-PD-1 antibody or antigen-binding fragment thereof and 200 mg, 300 mg, or 400 mg, or multiples thereof of the anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or the antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or the antigen-binding fragment thereof is 300 mg.

[0073] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) a 10-40 mM buffer (e.g., an acetate buffer or a histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or a pharmaceutically acceptable salt thereof, and / or sodium chloride), and (d) 0.1-1.2 mg / mL or 0.1-1 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:1-9, 1:1-8, 1:1-6, 1:1-5, or 1:1-4.5. , 1:1-4, 1:1-3.5, 1:1-3, 1:1-2.5, 1:1-2, 1:1-1.5, 1:1-1.25, 1:0.1-1, 1:0.4-1, or 1:0.8-1 (e.g., 9:1, 8:1, 6:1, 5:1, 4.5:1, 4:1, 3.5:1, 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1 , 1:1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:6, 1:8, 1:9), and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., acetate buffer or histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or pharmaceutically acceptable salts thereof, and / or sodium chloride), and (d) 0.1-1.2 mg / mL or 0.1-1 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1, 1:1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, or 1:6 (e.g., 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4), and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) a 10-40 mM buffer (e.g., a sodium acetate buffer, a histidine buffer, or a histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and / or arginine or a pharmaceutically acceptable salt thereof), and (d) 0.1-1.2 mg / mL or 0.1-1 mg / mL surfactant (e.g., polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody, or antigen-binding fragment thereof, to the anti-LAG-3 antibody, or antigen-binding fragment thereof, is 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In such specific embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 1-100 mg / mL, 1-80 mg / mL, 2-60 mg / mL, 3-30 mg / mL, 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 1-200 mg / mL, 2-160 mg / mL, 3-120 mg / mL, 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL.In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100-200 mg, or any multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or any multiples / fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, or a multiples / fraction thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or any multiples / fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or multiples thereof of the anti-PD-1 antibody or antigen-binding fragment thereof and 200 mg, 300 mg, or 400 mg, or multiples thereof of the anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or the antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or the antigen-binding fragment thereof is 300 mg.

[0074] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., acetate buffer or histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or pharmaceutically acceptable salts thereof, and / or sodium chloride), and (d) 0.2-0.8 mg / mL or 0.4-0.8 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:1-9, 1:1-8, 1:1-6, 1:1-5, or 1:1-4. 5, 1:1-4, 1:1-3.5, 1:1-3, 1:1-2.5, 1:1-2, 1:1-1.5, 1:1-1.25, 1:0.1-1, 1:0.4-1, or 1:0.8-1 (e.g., 9:1, 8:1, 6:1, 5:1, 4.5:1, 4:1, 3.5:1, 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1 , 1:1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:6, 1:8, 1:9), and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) a 10-20 mM buffer (e.g., an acetate buffer or a histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or a pharmaceutically acceptable salt thereof, and / or sodium chloride), and (d) 0.2-0.8 mg / mL or 0.4-0.8 mg / mL surfactant (e.g., polysorbate 60). wherein the fixed dose ratio of the anti-PD-1 antibody, or antigen-binding fragment thereof, to the anti-LAG-3 antibody, or antigen-binding fragment thereof, is 3:1, 2.5:1, 2:1, 1.5:1, 1.25:1, 1:1, 1:1.25, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, or 1:6 (e.g., 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4), and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) a 10-20 mM buffer (e.g., a sodium acetate buffer, a histidine buffer, or a histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and / or arginine or a pharmaceutically acceptable salt thereof), and (d) 0.2-0.8 mg / mL or 0.4-0. 8 mg / mL surfactant (e.g., polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody, or antigen-binding fragment thereof, to the anti-LAG-3 antibody, or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In such specific embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 1-100 mg / mL, 1-80 mg / mL, 2-60 mg / mL, 3-30 mg / mL, 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 1-200 mg / mL, 2-160 mg / mL, 3-120 mg / mL, 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL.In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100-200 mg, or any multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or any multiples / fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, or a multiples / fraction thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or any multiples / fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or multiples thereof of the anti-PD-1 antibody or antigen-binding fragment thereof and 200 mg, 300 mg, or 400 mg, or multiples thereof of the anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or the antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or the antigen-binding fragment thereof is 300 mg.

[0075] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., a histidine buffer or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 1-400 mg / mL sucrose and / or 10-1000 mM proline), and (d) 0.01-3 mg / mL surfactant ( For example, polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or multiples / fractions of any value within the range. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples / fractions thereof.In some embodiments, the pharmaceutical composition comprises 100 mg or multiples / fractions thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples / fractions thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg.

[0076] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 2-80 mM buffer (e.g., a histidine buffer or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 10-300 mg / mL sucrose and / or 50-800 mM proline), and (d) 0.04-2 mg / mL surfactant ( For example, polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or multiples / fractions of any value within the range. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples / fractions thereof.In some embodiments, the pharmaceutical composition comprises 100 mg or multiples / fractions thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples / fractions thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg.

[0077] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 5-60 mM buffer (e.g., a histidine buffer or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 20-200 mg / mL sucrose and / or 100-700 mM proline), and (d) 0.08-1.6 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or multiples / fractions of any value within the range. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples / fractions thereof.In some embodiments, the pharmaceutical composition comprises 100 mg or multiples / fractions thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples / fractions thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg.

[0078] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., a histidine buffer or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 40-200 mg / mL sucrose and / or 100-600 mM proline), and (d) 0.1-1.2 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or multiples / fractions of any value within the range. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples / fractions thereof.In some embodiments, the pharmaceutical composition comprises 100 mg or multiples / fractions thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples / fractions thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg.

[0079] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., a histidine buffer or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 40-180 mg / mL sucrose and / or 150-600 mM proline), and (d) 0.1-1 mg / mL surfactant (e.g., polysorbate 80 polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or multiples / fractions of any value within the range. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples / fractions thereof.In some embodiments, the pharmaceutical composition comprises 100 mg or multiples / fractions thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples / fractions thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg.

[0080] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., a histidine buffer or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 60-180 mg / mL sucrose and / or 200-600 mM proline), and (d) 0.2-0.8 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or multiples / fractions of any value within the range. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples / fractions thereof.In some embodiments, the pharmaceutical composition comprises 100 mg or multiples / fractions thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples / fractions thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg.

[0081] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., a histidine buffer or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 60-180 mg / mL or 70-170 mg / mL sucrose and / or 200-500 mM proline), and (d) 0.4-0.8 mg / mL of dapoxetine. L surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or multiples / fractions of any value within the range. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples / fractions thereof.In some embodiments, the pharmaceutical composition comprises 100 mg or multiples / fractions thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples / fractions thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg.

[0082] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., sodium acetate buffer, histidine buffer, or histidine-acetate buffer), (c) one or more stabilizers (e.g., 40-200 mg / mL sucrose), and (d) 0.1-1.2 mg / mL surfactant (e.g., polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., sodium acetate buffer, histidine buffer, or histidine-acetate buffer), (c) one or more stabilizers (e.g., 40-180 mg / mL sucrose), and (d) 0.1-1 mg / mL surfactant (e.g., polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) a 10-20 mM buffer (e.g., a sodium acetate buffer, a histidine buffer, or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 60-180 mg / mL sucrose), and (d) 0.2-0.8 mg / mL or 0.4-0.8 mg / mL of sucrose. m surfactant (e.g., polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody, or antigen-binding fragment thereof, to the anti-LAG-3 antibody, or antigen-binding fragment thereof, is 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or multiples / fractions of any value within the range. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples / fractions thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or multiples / fractions thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples / fractions thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg.

[0083] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., a histidine buffer or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 40-200 mg / mL sucrose and 100-600 mM proline), and (d) 0.1-1.2 mg / mL surfactant (e.g., polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., a histidine buffer or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 40-180 mg / mL sucrose and 150-600 mM proline), and (d) 0.1-1 mg / mL surfactant (e.g., polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL.In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or multiples / fractions of any value within the range. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples / fractions thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or multiples / fractions thereof of an anti-PD-1 antibody or antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples / fractions thereof of an anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg.

[0084] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., a histidine buffer or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 60-180 mg / mL sucrose and 200-600 mM proline), and (d) 0.2-0.8 mg / mL surfactant (e.g., polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0085] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., a histidine buffer or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 60-180 mg / mL or 70-170 mg / mL sucrose and 200-500 mM proline), and (d) 0.4-0.8 mM g / mL surfactant (e.g., polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody, or antigen-binding fragment thereof, to the anti-LAG-3 antibody, or antigen-binding fragment thereof, is 1.25:1, 1:1, 1:1.5, 1:2, 1:3, or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., a histidine buffer or a histidine-acetate buffer), (c) one or more stabilizers (e.g., 80-164.3 mg / mL sucrose and 200-300 mM proline), and (d) 0.4-0.8 mg / mL of PEG-100. wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mg / mL sucrose) and 200-500 mM proline (e.g., 200 mM, 1 ... In some embodiments, the present invention provides an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 70-170 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mg / mL sucrose) and 200-500 mM proline (e.g., 200 mM, 233 mM, 264 mM, 273 mM, 283 mM, 293 mM, 303 mM, 313 mM, 323 mM, 333 mM, 363 mM, 373 mM, 383 mM, 393 mM, 403 mM, 413 mM, 423 mM, 43 ... wherein the fixed dose ratio of the anti-PD-1 antibody, or antigen-binding fragment thereof, to the anti-LAG-3 antibody, or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 200-500 mM sucrose (e.g., 200 mM, 300 mM, 316 mM, 400 mM, or 500 mM sucrose) and 200-500 mM proline (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM, or 500 mM sucrose). 0 mM or 500 mM proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL or 0.8 mg / mL polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody, or antigen-binding fragment thereof, to the anti-LAG-3 antibody, or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8. In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 80-164.3 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mg / mL sucrose) and 200-300 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody, or antigen-binding fragment thereof, to the anti-LAG-3 antibody, or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 200 mM, 300 mM, 316 mM, 400 mM, or 480 mM sucrose) and 200-300 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline). M proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody, or antigen-binding fragment thereof, to the anti-LAG-3 antibody, or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 250-350 mM sucrose (e.g., 250 mM, 300 mM, 316 mM, or 350 mM sucrose) and 200-300 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline). acid), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody, or antigen-binding fragment thereof, to the anti-LAG-3 antibody, or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In such specific embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL.In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or multiples / fractions of any value within the range. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or multiples thereof of the anti-PD-1 antibody or antigen-binding fragment thereof and 200 mg, 300 mg, or 400 mg, or multiples thereof of the anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or the antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or the antigen-binding fragment thereof is 300 mg.

[0086] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 80-164.3 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mg / mL sucrose). ) and 200-300 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline), and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody, or antigen-binding fragment thereof, to the anti-LAG-3 antibody, or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 80-160 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, or 160 mg / mL sucrose) and 200-300 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline), and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5.3 to 5.8 or 5.5 to 5.8. In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 200 mM, 300 mM, 316 mM, 400 mM, or 480 mM sucrose) and 200-300 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline), and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5.3 to 5.8 or 5.5 to 5.8.In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 80-160 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, or 160 mg / mL sucrose) and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 310-320 mM sucrose (e.g., 316 mM sucrose) and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 108.1 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8. In such specific embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL.In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-30 mg / mL or 5-20 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5-10 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 5-15 mg / mL. In a specific embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 5 mg / mL, and the concentration of the anti-LAG-3 antibody or antigen-binding fragment thereof is 15 mg / mL. In a specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples / fractions thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160-800 mg, or 300-600 mg, or multiples / fractions of any value within the range. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg or multiples thereof, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or multiples thereof of the anti-PD-1 antibody or antigen-binding fragment thereof and 200 mg, 300 mg, or 400 mg, or multiples thereof of the anti-LAG-3 antibody or antigen-binding fragment thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 200 mg, and the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or the antigen-binding fragment thereof is 100 mg, and the mass of the anti-LAG-3 antibody or the antigen-binding fragment thereof is 300 mg.

[0087] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) a buffer, (c) one or more stabilizers, and (d) a surfactant.

[0088] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 1-100 mg / mL or 1-80 mg / mL anti-PD-1 antibody or an antigen-binding fragment thereof and 1-200 mg / mL or 2-160 mg / mL anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., acetate buffer or histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or a pharmaceutically acceptable salt thereof, and / or sodium chloride), and (d) 0.01-3 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0089] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 2-60 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 3-120 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 2-80 mM buffer (e.g., acetate buffer or histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or pharmaceutically acceptable salts thereof, and / or sodium chloride), and (d) 0.04-2 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0090] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 3-30 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 4-80 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 5-60 mM buffer (e.g., acetate buffer or histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or pharmaceutically acceptable salts thereof, and / or sodium chloride), and (d) 0.08-1.6 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0091] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 4-20 mg / mL or 5-20 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-50 mg / mL or 5-40 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., acetate buffer or histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or pharmaceutically acceptable salts thereof, and / or sodium chloride), and (d) 0.1-1.2 mg / mL or 0.1-1 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0092] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5-15 mg / mL or 5-10 mg / mL of an anti-PD-1 antibody or an antigen-binding fragment thereof and 5-30 mg / mL or 5-20 mg / mL of an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., an acetate buffer or a histidine buffer), (c) one or more stabilizers (e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or a pharmaceutically acceptable salt thereof, and / or sodium chloride), and (d) 0.2-0.8 mg / mL or 0.4-0.8 mg / mL of a surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0093] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 1-100 mg / mL or 1-80 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 1-200 mg / mL or 2-160 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., sodium acetate buffer, histidine buffer, or histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and / or arginine or pharmaceutically acceptable salts thereof), and (d) 0.01-3 mg / mL surfactant (e.g., polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0094] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 2-60 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 3-120 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 2-80 mM buffer (e.g., sodium acetate buffer, histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and / or arginine or pharmaceutically acceptable salts thereof), and (d) 0.04-2 mg / mL surfactant (e.g., polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0095] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 3-30 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 4-80 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 5-60 mM buffer (e.g., sodium acetate buffer, histidine buffer, or histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and / or arginine or pharmaceutically acceptable salts thereof), and (d) 0.08-1.6 mg / mL surfactant (e.g., polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0096] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 4-20 mg / mL or 5-20 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-50 mg / mL or 5-40 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., sodium acetate buffer, histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and / or arginine or pharmaceutically acceptable salts thereof), and (d) 0.1-1.2 mg / mL or 0.1-1 mg / mL surfactant (e.g., polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0097] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5-15 mg / mL or 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL or 5-20 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., sodium acetate buffer, histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and / or arginine or pharmaceutically acceptable salts thereof), and (d) 0.2-0.8 mg / mL or 0.4-0.8 mg / mL surfactant (e.g., polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0098] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 1-100 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 1-200 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., 1-400 mg / mL sucrose and / or 10-1000 mM proline), and (d) 0.01-3 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0099] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 1-80 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 2-160 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., 1-400 mg / mL sucrose and / or 10-1000 mM proline), and (d) 0.01-3 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0100] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 2-60 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 3-120 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 2-80 mM buffer (e.g., histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., 10-300 mg / mL sucrose and / or 50-800 mM proline), and (d) 0.04-2 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0101] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 3-30 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 4-80 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 5-60 mM buffer (e.g., histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., 20-200 mg / mL sucrose and / or 100-700 mM proline), and (d) 0.08-1.6 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0102] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 4-20 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-50 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., 40-200 mg / mL sucrose and / or 100-600 mM proline), and (d) 0.1-1.2 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0103] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5-20 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-40 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., 40-180 mg / mL sucrose and / or 150-600 mM proline), and (d) 0.1-1 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0104] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5-15 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., 60-180 mg / mL sucrose and / or 200-600 mM proline), and (d) 0.2-0.8 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0105] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-20 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., 60-180 mg / mL sucrose and / or 200-500 mM proline), and (d) 0.2-0.8 mg / mL or 0.4-0.8 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0106] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., 70-170 mg / mL sucrose and / or 200-500 mM proline), and (d) 0.4-0.8 mg / mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0107] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 4-20 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-50 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM sodium acetate buffer, histidine buffer or histidine-acetate buffer (e.g., 10 mM or 20 mM sodium acetate buffer, histidine buffer or histidine-acetate buffer), (c) 40-200 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL), In some embodiments, the pharmaceutical composition comprises (a) 0.1-1.2 mg / mL polysorbate 80 (e.g., 0.2 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and (b) 0.1-1.2 mg / mL polysorbate 80 (e.g., 0.2 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0108] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5-20 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-40 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM sodium acetate buffer, histidine buffer or histidine-acetate buffer (e.g., 10 mM or 20 mM sodium acetate buffer, histidine buffer or histidine-acetate buffer), (c) 40-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL). / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL or 164.3 mg / mL sucrose), and (d) 0.1-1 mg / mL polysorbate 80 (e.g., 0.2 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0109] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5-15 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM sodium acetate buffer, histidine buffer or histidine-acetate buffer (e.g., 10 mM or 20 mM sodium acetate buffer, histidine buffer or histidine-acetate buffer), (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL), In some embodiments, the pharmaceutical composition comprises (a) 0.2-0.8 mg / mL of polysorbate 80 (e.g., 0.2 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and (b) 0.2-0.8 mg / mL of polysorbate 80 (e.g., 0.2 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0110] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-20 mg / mL or 5-15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM sodium acetate buffer, histidine buffer or histidine-acetate buffer (e.g., 10 mM or 20 mM sodium acetate buffer, histidine buffer or histidine-acetate buffer), (c) 60-180 mg / mL or 70-170 mg / mL sucrose In some embodiments, the pharmaceutical composition comprises (a) 0.4-0.8 mg / mL of polysorbate 80 (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mg / mL sucrose), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0111] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 4-20 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-50 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM histidine buffer or histidine-acetate buffer (e.g., 10 mM or 20 mM histidine buffer or histidine-acetate buffer), (c) 40-200 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mM sucrose). g / mL sucrose) and 100-600 mM proline (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM, or 500 mM proline), and (d) 0.1-1.2 mg / mL polysorbate 80 (e.g., 0.2 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0112] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 5-20 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-40 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM histidine buffer or histidine-acetate buffer (e.g., 10 mM or 20 mM histidine buffer or histidine-acetate buffer), (c) 40-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mg / mL). In some embodiments, the pharmaceutical composition comprises (a) 1-20 mg / mL sucrose and (b) 150-600 mM proline (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM, or 500 mM proline), and (c) 0.1-1 mg / mL polysorbate 80 (e.g., 0.2 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0113] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 5-15 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer or histidine-acetate buffer (e.g., 10 mM or 20 mM histidine buffer or histidine-acetate buffer), (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mg / mL). g / mL sucrose) and 200-600 mM proline (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM or 500 mM proline), and (d) 0.2-0.8 mg / mL polysorbate 80 (e.g., 0.2 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0114] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-20 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer or histidine-acetate buffer (e.g., 10 mM or 20 mM histidine buffer or histidine-acetate buffer), (c) 60-180 mg / mL or 70-170 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mM sucrose). g / mL or 164.3 mg / mL sucrose) and 200-500 mM proline (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM or 500 mM proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0115] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 4-20 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-50 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-40 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 40-200 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mg / mL sucrose) and In some embodiments, the pharmaceutical composition comprises (a) 100-600 mM proline (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM or 500 mM proline), and (d) 0.1-1.2 mg / mL polysorbate 80 (e.g., 0.2 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0116] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 5-20 mg / mL of an anti-PD-1 antibody or an antigen-binding fragment thereof and 5-40 mg / mL of an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-40 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 40-180 mg / mL of sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mg / mL of sucrose) and 150-600 mM proline (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM or 500 mM proline), and (d) 0.1-1 mg / mL polysorbate 80 (e.g., 0.2 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0117] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5-15 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, In some embodiments, the pharmaceutical composition comprises (a) 200 mM proline (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM or 500 mM proline), and (b) 0.2-0.8 mg / mL polysorbate 80 (e.g., 0.2 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL or 0.8 mg / mL polysorbate 80); and the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0118] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mg / mL sucrose) and In some embodiments, the pharmaceutical composition comprises (a) 200-600 mM proline (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM or 500 mM proline), and (d) 0.2-0.8 mg / mL polysorbate 80 (e.g., 0.2 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0119] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mg / mL). In some embodiments, the pharmaceutical composition comprises (a) a 5-100 mM aqueous solution of at least one 5-80 mM sucrose and (b) 200-500 mM proline (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM, or 500 mM proline), and (c) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0120] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 80-164.3 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL or In some embodiments, the pharmaceutical composition comprises (a) 2-40 mg / mL sucrose (e.g., 164.3 mg / mL sucrose) and 200-300 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0121] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 80-160 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, or 160 mg / mL sucrose). In some embodiments, the present invention comprises (a) 2-4-hydroxy-3-thiazolinone (e.g., ...

[0122] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 200 mM, 300 mM, 316 mM, 400 mM, or 480 mM sucrose) and 200-30 0 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0123] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL or 1 In some embodiments, the pharmaceutical composition comprises (a) 200 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline) and (b) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0124] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 80-164.3 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL or In some embodiments, the pharmaceutical composition comprises (a) 2-40 mg / mL sucrose (e.g., 164.3 mg / mL sucrose) and 200-300 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0125] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 200 mM, 300 mM, 316 mM, 400 mM, or 480 mM sucrose) and 200-30 0 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0126] In some specific embodiments, the pharmaceutical compositions of the present disclosure comprise: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 80-160 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, or 160 mg / mL sucrose). In some embodiments, the present invention comprises (a) 2-4-hydroxy-3-thiazolinone (e.g., ...

[0127] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 12 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 4 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 In some embodiments, the pharmaceutical composition comprises (a) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and (b) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0128] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 12 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 4 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 80-164.3 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 16 In some embodiments, the pharmaceutical composition comprises (a) 0.0 mg / mL, 164 mg / mL, or 164.3 mg / mL sucrose, and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and (c) 0.1-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0129] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 In some embodiments, the pharmaceutical composition comprises (a) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and (b) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0130] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 80-164.3 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 16 In some embodiments, the pharmaceutical composition comprises (a) 0.0 mg / mL, 164 mg / mL, or 164.3 mg / mL sucrose, and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and (c) 0.1-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0131] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 7.5 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL). g / mL, 160 mg / mL, 164 mg / mL or 164.3 mg / mL sucrose), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0132] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL or 164.3 mg / mL sucrose). ) and 200-500 mM proline (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM or 500 mM proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0133] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL or 164.3 mg / mL sucrose) and 20 In some embodiments, the pharmaceutical composition comprises (a) 0-500 mM proline (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM or 500 mM proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8 or 5.5 to 5.8.

[0134] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 80-164.3 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL, or 164.3 mg / mL). / mL sucrose) and 200-300 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0135] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 200 mM, 300 mM, 316 mM, 400 mM, or 480 mM sucrose) and 200-300 mM proline ( For example, 200 mM, 233 mM, 250 mM, or 300 mM proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0136] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 80-164.3 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL). In some embodiments, the pharmaceutical composition comprises (a) 200 mM, 233 mM, 250 mM, or 300 mM proline, and (b) 0.8 mg / mL polysorbate 80; and (c) 0.8 mg / mL polysorbate 80; and the pharmaceutical composition has a pH of 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0137] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 200 mM, 300 mM, 316 mM, 400 mM, or 480 mM sucrose) and 200-300 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 mM proline), and (d) 0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0138] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 80-160 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, or 160 mg / mL sucrose) and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0139] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM sodium acetate buffer, (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL or 164.3 mg / mL sucrose), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0140] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM sodium acetate buffer, (c) 60-180 mg / mL sucrose (e.g., 80 mg / mL, 85.6 mg / mL, 100 mg / mL, 108.1 mg / mL, 160 mg / mL, 164 mg / mL or 164.3 mg / mL sucrose) and 200-500 mM proline In some embodiments, the pharmaceutical composition comprises (a) 2-4-hydroxy-3-thiazolyl glycolate (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM, or 500 mM proline), and (d) 0.4-0.8 mg / mL polysorbate 80 (e.g., 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, or 0.8 mg / mL polysorbate 80); and the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0141] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 80 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5.5 to 5.8.

[0142] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 80 mg / mL sucrose and 300 mM proline, and (d) 0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5.5 to 5.8.

[0143] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 160 mg / mL or 164.3 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5.5 to 5.8.

[0144] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 4-6 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 12-18 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 18-24 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 80-120 mg / mL sucrose (e.g., 108.1 mg / mL sucrose) and 180-240 mM proline (e.g., 200 mM proline), and (d) 0.7-0.9 mg / mL polysorbate 80 (e.g., 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5.5 to 5.8.

[0145] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 4-6 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 12-18 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 18-24 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 100-120 mg / mL sucrose (e.g., 108.1 mg / mL sucrose) and 180-240 mM proline (e.g., 200 mM proline), and (d) 0.7-0.9 mg / mL polysorbate 80 (e.g., 0.8 mg / mL polysorbate 80); and the pH of the pharmaceutical composition is 5.5 to 5.8.

[0146] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 108.1 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5.5 to 5.8.

[0147] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 316 mM sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5.5 to 5.8.

[0148] In some specific embodiments, the pharmaceutical composition of the present disclosure comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 108.1 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5.8.

[0149] In some embodiments, the pharmaceutical compositions of the present disclosure can be stably stored at 2-8°C for at least about 1 week, at least about 2 weeks, at least about 1 month, at least about 2 months, at least about 3 months, at least about 6 months, at least about 9 months, at least about 1 year, or at least about 2 years. In some embodiments, the pharmaceutical compositions of the present disclosure can be stably stored at 25°C for at least about 1 week, at least about 2 weeks, at least about 1 month, at least about 2 months, at least about 3 months, at least about 6 months, at least about 9 months, at least about 1 year, or at least about 2 years. In some embodiments, the pharmaceutical compositions of the present disclosure can be stably stored at 40°C for at least about 1 week, at least about 2 weeks, at least about 1 month, at least about 2 months, at least about 3 months, at least about 6 months, at least about 9 months, at least about 1 year, or at least about 2 years.

[0150] Lyophilized preparations

[0151] The present disclosure also provides a lyophilized formulation comprising an anti-PD-1 antibody or an antigen-binding fragment thereof and a second antibody or an antigen-binding fragment thereof. In some embodiments, the second antibody or an antigen-binding fragment thereof is an anti-LAG-3 antibody or an antigen-binding fragment thereof.

[0152] The present disclosure also provides a method for preparing the lyophilized formulation, which includes the step of freeze-drying the pharmaceutical composition of the present disclosure. In some embodiments, the freeze-drying is carried out according to methods well known in the art, including but not limited to the steps of pre-freezing, primary drying and secondary drying. It will be understood by those skilled in the art that any method of removing water from the pharmaceutical composition of the present disclosure is applicable to the present disclosure. It will be understood by those skilled in the art that in the pharmaceutical field, lyophilized formulations typically have a residual moisture content of about 0.1 to 5% (w / v) and are present as a powder or a physically stable cake.

[0153] The present disclosure also provides a lyophilized preparation comprising an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, wherein the lyophilized preparation is prepared by the aforementioned method for preparing a lyophilized preparation.

[0154] The present disclosure also provides a lyophilized formulation comprising an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, which, upon reconstitution, can form the pharmaceutical composition of the present disclosure. In some embodiments, the solution used for reconstitution includes, but is not limited to, water for injection, sodium chloride injection, Ringer's solution, or dextrose injection. In the present disclosure, "reconstitution" and "reconstitution" are used interchangeably.

[0155] Anti-PD-1 antibodies or antigen-binding fragments thereof

[0156] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof described herein comprises: a HCDR1 having an amino acid sequence as set forth in SEQ ID NO: 11, a HCDR2 having an amino acid sequence as set forth in SEQ ID NO: 12, a HCDR3 having an amino acid sequence as set forth in SEQ ID NO: 13, a LCDR1 having an amino acid sequence as set forth in SEQ ID NO: 14, a LCDR2 having an amino acid sequence as set forth in SEQ ID NO: 15, and a LCDR3 having an amino acid sequence as set forth in SEQ ID NO: 16 (disclosed in CN106977602A, the entire contents of which are incorporated herein by reference). In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having an amino acid sequence as set forth in SEQ ID NO: 17, and LCDR1, LCDR2, and LCDR3 in the light chain variable region having an amino acid sequence as set forth in SEQ ID NO: 18. The CDR sequences of the anti-PD-1 antibody or antigen-binding fragment thereof are shown in Table 1.

[0157] Table 1. CDR sequences of anti-PD-1 antibodies or antigen-binding fragments thereof

[0158] It will be understood by those skilled in the art that, unless otherwise specified, the term "CDR" or "complementarity determining region" of a given antibody or region thereof (e.g., variable region) should be understood to encompass complementarity determining regions defined by any known scheme. Although CDR regions are shown in Table 1, when referring to antibodies defined by specific CDR sequences, the scope of the antibodies encompasses antibodies defined by CDR sequences defined by any numbering scheme (e.g., a combination of one or more of the AbM, Kabat, CCG, Chothia, IMGT, or Contact definitions known in the art).

[0159] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 17. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region set forth in SEQ ID NO: 17. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain variable region set forth in SEQ ID NO: 18. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 17, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 17, and a light chain variable region having the amino acid sequence of SEQ ID NO: 18. In some specific embodiments, the amino acid sequence of the heavy chain variable region of the anti-PD-1 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 17, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO: 18.

[0160] In some embodiments, the anti-PD-1 antibodies or antigen-binding fragments thereof described in the present disclosure comprise a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3, and the light chain variable region comprises LCDR1, LCDR2, and LCDR3, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, LCDR1 comprises the amino acid sequence of SEQ ID NO: 14, LCDR2 comprises the amino acid sequence of SEQ ID NO: 15, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 16, and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 17. NO:17 has an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:18.

[0161] In some embodiments, the anti-PD-1 antibody or its antigen-binding fragment may further comprise an immunoglobulin constant region, or a fragment, analog, variant or derivative of the constant region. In some embodiments, the constant region comprises a heavy chain constant region and a light chain constant region. In some embodiments, the heavy chain constant region is from a human immunoglobulin heavy chain, such as IgG1, IgG2, IgG3 and IgG4 or other classes of immunoglobulin heavy chains, preferably IgG1 heavy chains. In some embodiments, the light chain constant region is from a human immunoglobulin light chain, such as a kappa light chain or a lambda light chain of a human immunoglobulin. In some embodiments, the constant region may comprise any modification described in the text, such as insertion, deletion, substitution or chemical modification of amino acids. In some embodiments, the constant region comprises a mutation that alters effector function. In some embodiments, any amino acid residue in the constant region may be substituted with an amino acid residue of any allotype.

[0162] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises the heavy chain set forth in SEQ ID NO: 19. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises the light chain set forth in SEQ ID NO: 20. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19, and a light chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence as set forth in SEQ ID NO: 19, and a light chain having an amino acid sequence as set forth in SEQ ID NO: 20. In some specific embodiments, the heavy chain amino acid sequence of the anti-PD-1 antibody or antigen-binding fragment thereof is as set forth in SEQ ID NO: 19, and the light chain amino acid sequence is as set forth in SEQ ID NO: 20. The terminal amino acid K of SEQ ID NO: 19 may or may not be present.

[0163] Anti-LAG-3 antibodies or antigen-binding fragments thereof

[0164] In some embodiments, the anti-LAG-3 antibodies or antigen-binding fragments thereof described herein comprise a heavy chain CDR1 (HCDR1) of the amino acid sequence set forth in SEQ ID NO: 1 or 21, a HCDR2 of the amino acid sequence set forth in SEQ ID NO: 2 or 22, a HCDR3 of the amino acid sequence set forth in SEQ ID NO: 3 or 23, a light chain CDR1 (LCDR1) of the amino acid sequence set forth in SEQ ID NO: 4 or 24, a LCDR2 of the amino acid sequence set forth in SEQ ID NO: 5 or 25, and a LCDR3 of the amino acid sequence set forth in SEQ ID NO: 6 or 26. In some embodiments, the anti-LAG-3 antibodies or antigen-binding fragments thereof described herein comprise a HCDR1 of the amino acid sequence set forth in SEQ ID NO: 1, a HCDR2 of the amino acid sequence set forth in SEQ ID NO: 2, a HCDR3 of the amino acid sequence set forth in SEQ ID NO: 3, a LCDR1 of the amino acid sequence set forth in SEQ ID NO: 4, a LCDR2 of the amino acid sequence set forth in SEQ ID NO: 5, and a LCDR3 of the amino acid sequence set forth in SEQ ID NO: 6. In some embodiments, the anti-LAG-3 antibodies or antigen-binding fragments thereof described herein comprise: a HCDR1 having an amino acid sequence as set forth in SEQ ID NO:21, a HCDR2 having an amino acid sequence as set forth in SEQ ID NO:22, a HCDR3 having an amino acid sequence as set forth in SEQ ID NO:23, a LCDR1 having an amino acid sequence as set forth in SEQ ID NO:24, a LCDR2 having an amino acid sequence as set forth in SEQ ID NO:25, and a LCDR3 having an amino acid sequence as set forth in SEQ ID NO:26. In some embodiments, the anti-LAG-3 antibodies or antigen-binding fragments thereof described herein comprise: HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having an amino acid sequence as set forth in SEQ ID NO:7, and LCDR1, LCDR2, and LCDR3 in the light chain variable region having an amino acid sequence as set forth in SEQ ID NO:8. The CDR sequences of the anti-LAG-3 antibodies or antigen-binding fragments thereof are shown in Table 2 (disclosed in CN110062766A, the entire contents of which are incorporated herein by reference).

[0165] Table 2. CDR sequences of anti-LAG-3 antibodies or antigen-binding fragments thereof

[0166] It will be understood by those skilled in the art that, unless otherwise specified, the term "CDR" or "complementarity determining region" of a given antibody or region thereof (e.g., variable region) should be understood to encompass complementarity determining regions defined by any known scheme. Although CDR regions are shown in Table 2, when referring to antibodies defined by specific CDR sequences, the scope of the antibodies encompasses antibodies defined by CDR sequences defined by any numbering scheme (e.g., a combination of one or more of the AbM, Kabat, CCG, Chothia, IMGT, or Contact definitions known in the art).

[0167] In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 7 or 27. In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 8 or 28. In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises the heavy chain variable region set forth in SEQ ID NO: 7. In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises the light chain variable region set forth in SEQ ID NO: 8. In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region that has an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:7 or 27, and a light chain variable region that has an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:8 or 28. In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 7, and a light chain variable region having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 27, and a light chain variable region having the amino acid sequence of SEQ ID NO: 28. In specific embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 7, and a light chain variable region having the amino acid sequence of SEQ ID NO: 8.In some specific embodiments, the amino acid sequence of the heavy chain variable region of the anti-LAG-3 antibody or antigen-binding fragment thereof is shown in SEQ ID NO:27, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO:28.

[0168] In some embodiments, the anti-LAG-3 antibodies or antigen-binding fragments thereof of the present disclosure comprise a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3, and the light chain variable region comprises LCDR1, LCDR2, and LCDR3, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO:1, HCDR2 comprises the amino acid sequence of SEQ ID NO:2, HCDR3 comprises the amino acid sequence of SEQ ID NO:3, LCDR1 comprises the amino acid sequence of SEQ ID NO:4, LCDR2 comprises the amino acid sequence of SEQ ID NO:5, and LCDR3 comprises the amino acid sequence of SEQ ID NO:6, and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:7. NO:7 having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:8.

[0169] In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof may further comprise an immunoglobulin constant region, or a fragment, analog, variant, or derivative of such a constant region. In some embodiments, the constant region comprises a heavy chain constant region and a light chain constant region. In some embodiments, the heavy chain constant region is derived from a human immunoglobulin heavy chain, such as an IgG1, IgG2, IgG3, or IgG4 heavy chain or other class of immunoglobulins, preferably an IgG4 heavy chain. In some embodiments, the light chain constant region is derived from a human immunoglobulin light chain, such as a kappa light chain or a lambda light chain of a human immunoglobulin. In some embodiments, the constant region may comprise any modification described herein, such as an insertion, deletion, substitution, or chemical modification of amino acids. In some embodiments, the constant region comprises a mutation that alters effector function. In some embodiments, any amino acid residue in the constant region may be substituted with an amino acid residue of any allotype.

[0170] In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 9 or 29. In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises a light chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 10 or 30. In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises the heavy chain set forth in SEQ ID NO: 9. In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises the light chain set forth in SEQ ID NO: 10. In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises a heavy chain that has an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 9 or 29, and a light chain that has an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 10 or 30. In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises a heavy chain having the amino acid sequence of SEQ ID NO: 9, and a light chain having the amino acid sequence of SEQ ID NO: 10. In some embodiments, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises a heavy chain having the amino acid sequence of SEQ ID NO: 29, and a light chain having the amino acid sequence of SEQ ID NO: 30. In some specific embodiments, the heavy chain of the anti-LAG-3 antibody or antigen-binding fragment thereof has the amino acid sequence of SEQ ID NO: 9, and the light chain has the amino acid sequence of SEQ ID NO: 10. In some specific embodiments, the heavy chain of the anti-LAG-3 antibody or antigen-binding fragment thereof has the amino acid sequence of SEQ ID NO: 29, and the light chain has the amino acid sequence of SEQ ID NO: 30.The terminal amino acid K of SEQ ID NOs: 9 and 29 may be present or absent.

[0171] Preparation method of pharmaceutical composition

[0172] The present disclosure relates to any method of preparing the pharmaceutical composition of the present disclosure.

[0173] In some embodiments, the present disclosure provides a method for preparing a pharmaceutical composition of the present disclosure, comprising: mixing a pharmaceutical composition comprising an anti-LAG-3 antibody or antigen-binding fragment thereof with a pharmaceutical composition comprising an anti-PD-1 antibody or antigen-binding fragment thereof in a desired ratio. In some embodiments, the pharmaceutical composition of the antibody or antigen-binding fragment thereof comprises the antibody or antigen-binding fragment thereof and a buffer, and optionally, further comprises a stabilizer and a surfactant.

[0174] In some embodiments, the present disclosure provides a method for preparing a pharmaceutical composition of the present disclosure, comprising: contacting an anti-LAG-3 antibody or antigen-binding fragment thereof with a buffer, a stabilizer, and a surfactant, contacting an anti-PD-1 antibody or antigen-binding fragment thereof with a buffer, a stabilizer, and a surfactant, and mixing the two in a desired ratio. In some embodiments, the step of contacting the antibody or antigen-binding fragment thereof with the buffer, the stabilizer, and the surfactant comprises displacing the antibody or antigen-binding fragment thereof into the buffer, followed by adding the surfactant and the stabilizer, wherein the surfactant and the stabilizer are added in any order.

[0175] It is understood that the preparation method of the present disclosure may further include the steps of sterilizing and packaging the prepared pharmaceutical composition (e.g., packaging into vials). The present disclosure does not specifically limit the sterilization method, and membrane filtration may be used but is not limited thereto.

[0176] In some embodiments, the buffer comprises a phosphate buffer, a histidine buffer, an acetate buffer, or a citrate buffer. In some embodiments, the stabilizer comprises a sugar alcohol, a disaccharide, a monosaccharide, an amino acid, or a salt. In some embodiments, the surfactant comprises a polysorbate, a poloxamer, or a polyethylene glycol.

[0177] use

[0178] The present disclosure provides a method of treating a disease in a subject, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition or lyophilized formulation of the present disclosure.

[0179] The present disclosure provides a method for enhancing an immune response in a subject, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition or lyophilized formulation of the present disclosure. The present disclosure also provides a use of the pharmaceutical composition or lyophilized formulation of the present disclosure in the preparation of a medicament for enhancing an immune response in a subject.

[0180] The present disclosure provides a method for inducing or enhancing an anti-tumor immune response, the method comprising administering a therapeutically effective amount of a pharmaceutical composition or lyophilized formulation of the present disclosure to a subject. The present disclosure also provides the use of the pharmaceutical composition and lyophilized formulation of the present disclosure in the preparation of a medicament for inducing or enhancing an anti-tumor immune response.

[0181] The present disclosure provides a method for treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition or lyophilized formulation of the present disclosure. The present disclosure also provides use of the pharmaceutical composition or lyophilized formulation of the present disclosure in preparing a medicament for treating cancer in a subject.

[0182] The term "cancer" is the name of a disease in which the cells of the body become abnormal and divide and grow uncontrollably. In some embodiments, the cancer is a recurrent, refractory, metastatic, and / or advanced cancer. In some embodiments, the cancer is a non-solid tumor. In some embodiments, the cancer is a solid tumor. In some embodiments, the cancer includes but is not limited to head and neck cancer, nasopharyngeal cancer, oral cancer, esophageal cancer, lung cancer, liver cancer, colon cancer, colorectal cancer, kidney cancer, endometrial cancer, cervical cancer, glioblastoma, bladder cancer, breast cancer, ovarian cancer, fallopian tube cancer, prostate cancer, anal cancer, testicular cancer, vaginal cancer, stomach cancer, gastroesophageal junction cancer, pancreatic cancer, bone cancer, thyroid cancer, skin cancer, nervous system tumors, sarcomas, myeloma, bile duct cancer, gallbladder cancer, soft tissue sarcomas, lymphomas, and hematologic tumors.

[0183] In some embodiments, the head and neck cancer comprises head and neck squamous cell carcinoma. In some embodiments, the esophageal cancer comprises esophageal squamous cell carcinoma. In some embodiments, the lung cancer comprises small cell lung cancer and non-small cell lung cancer. In some embodiments, the liver cancer comprises hepatocellular carcinoma. In some embodiments, the kidney cancer comprises renal cell carcinoma. In some embodiments, the bladder cancer comprises urothelial carcinoma. In some embodiments, the skin cancer comprises melanoma.

[0184] In some embodiments, the lymphoma comprises Hodgkin lymphoma and non-Hodgkin lymphoma. In some embodiments, the lymphoma comprises T-cell non-Hodgkin lymphoma or B-cell non-Hodgkin lymphoma. In some embodiments, the non-Hodgkin lymphoma comprises primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, peripheral T-cell lymphoma, mantle cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, cutaneous T-cell lymphoma, cutaneous B-cell lymphoma, marginal zone lymphoma, and / or AIDS-related B-cell lymphoma.

[0185] In some embodiments, the bloodstream comprises myeloma, leukemia, myelodysplastic syndrome, myelofibrosis, and B-cell malignancies. In some embodiments, the leukemia comprises acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and chronic myelomonocytic leukemia.

[0186] In some embodiments, the pharmaceutical compositions or lyophilized formulations of the present disclosure can be administered together with cancer therapeutics known in the art, such as immunotherapeutics, chemotherapy, radiotherapy, cytokines, and the like.

[0187] The present disclosure provides a method for treating an infectious disease of a subject, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition or a lyophilized formulation of the present disclosure. The present disclosure also provides the use of the pharmaceutical composition and lyophilized formulation of the present disclosure in the preparation of a medicament for treating an infectious disease. In some embodiments, the infectious disease is a disease caused by organisms such as bacteria, fungi, parasites, viruses or other pathogens, including but not limited to AIDS, viral hepatitis, viral pneumonia, hand, foot and mouth disease, meningitis, measles, etc. In some embodiments, the pharmaceutical composition or lyophilized formulation of the present disclosure can be administered together with an infectious disease therapeutic agent known in the art, such as a vaccine.

[0188] The pharmaceutical compositions and lyophilized formulations of the present disclosure can be administered according to methods known in the art. In some embodiments, the lyophilized formulation requires reconstitution prior to administration to obtain a reconstituted solution of the lyophilized formulation. In some embodiments, reconstitution can be performed with water for injection, sodium chloride injection, Ringer's solution, or dextrose injection.

[0189] In some embodiments, pharmaceutical compositions of the present disclosure and lyophilized formulations are suitable for parenteral administration. In some embodiments, pharmaceutical compositions of the present disclosure and lyophilized formulations are suitable for intravenous, intramuscular, intraperitoneal, subcutaneous, epidermal, spinal, intralesional injection or infusion. In some embodiments, pharmaceutical compositions of the present disclosure and lyophilized formulations are suitable for topical administration, inhalation, oral administration or administration by sustained release or delayed release delivery systems. In some embodiments, pharmaceutical compositions of the present disclosure, lyophilized formulations, and the reconstituted solution of lyophilized formulations can be diluted with a suitable diluent before administration. In some embodiments, water for injection, sodium chloride injection, Ringer's solution, or glucose injection can be diluted.

[0190] Medical devices, kits, and vials

[0191] The present disclosure also provides a medicine box or vial containing the pharmaceutical composition or lyophilized formulation of the present disclosure. The medicine box and vial of the present disclosure may also contain instructions for using the pharmaceutical composition or lyophilized formulation of the present disclosure to treat a disease. The vial is a single chamber (containing a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof).

[0192] The present disclosure also provides a medical device comprising a pharmaceutical composition or lyophilized formulation of the present disclosure. The medical device of the present disclosure may also include instructions for use of the pharmaceutical composition or lyophilized formulation of the present disclosure in treating a disease. In some embodiments, the medical device comprises a syringe and an intravenous bag. The syringe or intravenous bag is single-lumen (containing a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof).

[0193] In some embodiments, the disease comprises cancer. In some embodiments, the cancer is recurrent, refractory, metastatic and / or advanced cancer. In some embodiments, the cancer is a non-solid tumor. In some embodiments, the cancer is a solid tumor. In some embodiments, the cancer includes but is not limited to head and neck cancer, nasopharyngeal cancer, oral cancer, esophageal cancer, lung cancer, liver cancer, colon cancer, colorectal cancer, kidney cancer, endometrial cancer, cervical cancer, glioblastoma, bladder cancer, breast cancer, ovarian cancer, fallopian tube cancer, prostate cancer, anal cancer, testicular cancer, vaginal cancer, gastric cancer, gastroesophageal junction cancer, pancreatic cancer, bone cancer, thyroid cancer, skin cancer, nervous system tumors, sarcomas, myeloma, bile duct cancer, gallbladder cancer, soft tissue sarcomas, lymphomas and hematological tumors.

[0194] In some embodiments, the head and neck cancer comprises head and neck squamous cell carcinoma. In some embodiments, the esophageal cancer comprises esophageal squamous cell carcinoma. In some embodiments, the lung cancer comprises small cell lung cancer and non-small cell lung cancer. In some embodiments, the liver cancer comprises hepatocellular carcinoma. In some embodiments, the kidney cancer comprises renal cell carcinoma. In some embodiments, the bladder cancer comprises urothelial carcinoma. In some embodiments, the skin cancer comprises melanoma.

[0195] In some embodiments, the lymphoma comprises Hodgkin lymphoma and non-Hodgkin lymphoma. In some embodiments, the lymphoma comprises T-cell non-Hodgkin lymphoma or B-cell non-Hodgkin lymphoma. In some embodiments, the non-Hodgkin lymphoma comprises primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, peripheral T-cell lymphoma, mantle cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, cutaneous T-cell lymphoma, cutaneous B-cell lymphoma, marginal zone lymphoma, and / or AIDS-related B-cell lymphoma.

[0196] In some embodiments, the bloodstream comprises myeloma, leukemia, myelodysplastic syndrome, myelofibrosis, and B-cell malignancies. In some embodiments, the leukemia comprises acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and chronic myelomonocytic leukemia.

[0197] In some embodiments, the disease includes an infectious disease. In some embodiments, the infectious disease is a disease caused by organisms such as bacteria, fungi, parasites, viruses, or other pathogens, including but not limited to AIDS, viral hepatitis, viral pneumonia, hand, foot and mouth disease, meningitis, measles, etc.

[0198] The pharmaceutical compositions of the present disclosure can be provided in any desired volume. In some embodiments, the pharmaceutical compositions of the present disclosure are present in a single cavity of a medicine box, a vial, a syringe, or an intravenous bag with a fill volume of 1 mL, 2 mL, 5 mL, 10 mL, or 20 mL. In some embodiments, the pharmaceutical compositions of the present disclosure are present in a single cavity of a vial, a syringe, or an intravenous bag with a fill volume of 30 mL or 40 mL.

[0199] The present disclosure also provides the following specific implementation schemes, but the protection scope of the present disclosure is not limited thereto:

[0200] Embodiment 1. A pharmaceutical composition comprising (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) a buffer, (c) one or more stabilizers, and (d) a surfactant.

[0201] Embodiment 2. The pharmaceutical composition of embodiment 1, wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:1-9, 1:1-8, 1:1-6, 1:1-5, 1:1-4.5, 1:1-4, 1:1-3.5, 1:1-3, 1:1-2.5, 1:1-2, 1:1-1.5, 1:1-1.25, 1:0.1-1, 1:0.4-1, or 1:0.8-1.

[0202] Embodiment 3. The pharmaceutical composition of embodiment 1 or 2, wherein the anti-PD-1 antibody or antigen-binding fragment thereof is at a concentration of 1-100 mg / mL, 1-80 mg / mL, 2-60 mg / mL, 3-30 mg / mL, 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL.

[0203] Embodiment 4. The pharmaceutical composition of any one of Embodiments 1-3, wherein the anti-LAG-3 antibody or antigen-binding fragment thereof is at a concentration of 1-200 mg / mL, 2-160 mg / mL, 3-120 mg / mL, 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL.

[0204] Embodiment 5. The pharmaceutical composition according to any one of Embodiments 1-4, wherein the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100-200 mg.

[0205] Embodiment 6. The pharmaceutical composition of any one of Embodiments 1-5, wherein the mass of the anti-LAG-3 antibody or antigen-binding fragment thereof is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg.

[0206] Embodiment 7. The pharmaceutical composition according to embodiments 1-6, wherein the buffer comprises histidine buffer, acetate buffer, Tris buffer, phosphate buffer or citrate buffer.

[0207] Embodiment 8. The pharmaceutical composition of any one of embodiments 1-7, wherein the concentration of the buffer is 1-100 mM, 2-80 mM, 5-60 mM, 10-40 mM or 10-20 mM.

[0208] Embodiment 9. The pharmaceutical composition according to any one of embodiments 1-8, wherein the pharmaceutical composition comprises 1-100 mM, 2-80 mM, 5-60 mM, 10-40 mM, or 10-20 mM histidine buffer.

[0209] Embodiment 10. The pharmaceutical composition according to any one of Embodiments 1-9, wherein the stabilizer comprises mannitol, sorbitol, trehalose, sucrose, maltose, lactose, lysine, glycine, proline, arginine or a pharmaceutically acceptable salt thereof, or sodium chloride; preferably, the stabilizer comprises sucrose, proline, or arginine or a pharmaceutically acceptable salt thereof.

[0210] Embodiment 11. The pharmaceutical composition of any one of Embodiments 1-10, wherein the pharmaceutical composition comprises 1-400 mg / mL, 10-300 mg / mL, 20-200 mg / mL, 40-200 mg / mL, 40-180 mg / mL, 60-180 mg / mL, or 70-170 mg / mL of sucrose.

[0211] Embodiment 12. The pharmaceutical composition of any one of embodiments 1-11, wherein the pharmaceutical composition comprises 10-1000 mM, 50-800 mM, 100-700 mM, 100-600 mM, 150-600 mM, 200-600 mM, 200-500 mM, or 200-300 mM proline.

[0212] Embodiment 13. The pharmaceutical composition of any one of embodiments 1-12, wherein the pharmaceutical composition comprises 1-400 mg / mL, 10-300 mg / mL, 20-200 mg / mL, 40-200 mg / mL, 40-180 mg / mL, 60-180 mg / mL, or 70-170 mg / mL of sucrose and 10-1000 mM, 50-800 mM, 100-700 mM, 100-600 mM, 150-600 mM, 200-600 mM, 200-500 mM, or 200-300 mM proline.

[0213] Embodiment 14. The pharmaceutical composition of any one of Embodiments 1-13, wherein the surfactant comprises polysorbate 80 or polysorbate 20.

[0214] Embodiment 15. The pharmaceutical composition of any one of Embodiments 1-14, wherein the concentration of the surfactant is 0.01-3 mg / mL, 0.04-2 mg / mL, 0.08-1.6 mg / mL, 0.1-1.2 mg / mL, 0.1-1 mg / mL, 0.2-0.8 mg / mL, or 0.4-0.8 mg / mL.

[0215] Embodiment 16. The pharmaceutical composition of any one of Embodiments 1-15, wherein the pharmaceutical composition comprises 0.01-3 mg / mL, 0.04-2 mg / mL, 0.08-1.6 mg / mL, 0.1-1.2 mg / mL, 0.1-1 mg / mL, 0.2-0.8 mg / mL, or 0.4-0.8 mg / mL of polysorbate 80.

[0216] Embodiment 17. The pharmaceutical composition of any one of Embodiments 1-16, wherein the pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.8.

[0217] Embodiment 18. The pharmaceutical composition of any one of Embodiments 1-17, wherein the pharmaceutical composition comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 1-100 mM histidine buffer, (c) 1-400 mg / mL sucrose and 10-1000 mM proline, and (d) 0.01-3 mg / mL polysorbate 80 or polysorbate 20; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.3.

[0218] Embodiment 19. The pharmaceutical composition of any one of Embodiments 1-18, wherein the pharmaceutical composition comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer, (c) 60-180 mg / mL sucrose and 200-500 mM proline, and (d) 0.4-0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3.

[0219] Embodiment 20. The pharmaceutical composition of any one of Embodiments 1-19, wherein the pharmaceutical composition comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer, (c) 80-164.3 mg / mL sucrose and 200-300 mM proline, and (d) 0.4-0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3.

[0220] Embodiment 21. The pharmaceutical composition of any one of Embodiments 1-20, wherein the pharmaceutical composition comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer, (c) 80-164.3 mg / mL sucrose and 200-300 mM proline, and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3.

[0221] Embodiment 22. The pharmaceutical composition of any one of Embodiments 1-21, wherein the pharmaceutical composition comprises: (a) an anti-PD-1 antibody or antigen-binding fragment thereof and an anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer, (c) 80-160 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3.

[0222] Embodiment 23. The pharmaceutical composition of any one of Embodiments 1-22, wherein the pharmaceutical composition comprises: (b) 20 mM histidine buffer, (c) 108.1 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3.

[0223] Embodiment 24. The pharmaceutical composition of any one of Embodiments 1-23, wherein the pharmaceutical composition comprises: (a) 1-100 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 1-200 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 1-100 mM histidine buffer, (c) 1-400 mg / mL sucrose and 10-1000 mM proline, and (d) 0.01-3 mg / mL polysorbate 80 or polysorbate 20; and the pH of the pharmaceutical composition is 5 to 6.3.

[0224] Embodiment 25. The pharmaceutical composition of any one of Embodiments 1-24, wherein the pharmaceutical composition comprises: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer, (c) 60-180 mg / mL sucrose and 200-500 mM proline, and (d) 0.4-0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5 to 6.3.

[0225] Embodiment 26. The pharmaceutical composition of any one of Embodiments 1-25, wherein the pharmaceutical composition comprises: (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer, (c) 80-164.3 mg / mL sucrose and 200-300 mM proline, and (d) 0.4-0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5 to 6.3.

[0226] Embodiment 27. The pharmaceutical composition of any one of Embodiments 1-26, wherein the pharmaceutical composition comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer, (c) 80-164.3 mg / mL sucrose and 200-300 mM proline, and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3.

[0227] Embodiment 28. The pharmaceutical composition of any one of Embodiments 1-27, wherein the pharmaceutical composition comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer, (c) 80-160 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5 to 6.3.

[0228] Embodiment 29. The pharmaceutical composition of any one of Embodiments 1-28, wherein the pharmaceutical composition comprises: (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer, (c) 108.1 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5 to 6.3.

[0229] Embodiment 30. The pharmaceutical composition of any one of Embodiments 1-29, wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises: a HCDR1 with the amino acid sequence set forth in SEQ ID NO: 11, a HCDR2 with the amino acid sequence set forth in SEQ ID NO: 12, a HCDR3 with the amino acid sequence set forth in SEQ ID NO: 13, a LCDR1 with the amino acid sequence set forth in SEQ ID NO: 14, a LCDR2 with the amino acid sequence set forth in SEQ ID NO: 15, and a LCDR3 with the amino acid sequence set forth in SEQ ID NO: 16.

[0230] Embodiment 31. The pharmaceutical composition of any one of Embodiments 1-30, wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 17, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 18.

[0231] Embodiment 32. The pharmaceutical composition of any one of Embodiments 1-31, wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises: a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 19, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 20.

[0232] Embodiment 33. The pharmaceutical composition of any one of Embodiments 1-32, wherein the anti-LAG-3 antibody or antigen-binding fragment thereof comprises: a HCDR1 of the amino acid sequence set forth in SEQ ID NO: 1, a HCDR2 of the amino acid sequence set forth in SEQ ID NO: 2, a HCDR3 of the amino acid sequence set forth in SEQ ID NO: 3, a LCDR1 of the amino acid sequence set forth in SEQ ID NO: 4, a LCDR2 of the amino acid sequence set forth in SEQ ID NO: 5, and a LCDR3 of the amino acid sequence set forth in SEQ ID NO: 6; or a HCDR1 of the amino acid sequence set forth in SEQ ID NO: 21, a HCDR2 of the amino acid sequence set forth in SEQ ID NO: 22, a HCDR3 of the amino acid sequence set forth in SEQ ID NO: 23, a LCDR1 of the amino acid sequence set forth in SEQ ID NO: 24, a LCDR2 of the amino acid sequence set forth in SEQ ID NO: 25, and a LCDR3 of the amino acid sequence set forth in SEQ ID NO: 26.

[0233] Embodiment 34. The pharmaceutical composition of any one of Embodiments 1-33, wherein the anti-LAG-3 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:8; or a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:27, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:28.

[0234] Embodiment 35. The pharmaceutical composition of any one of Embodiments 1-34, wherein the anti-LAG-3 antibody or antigen-binding fragment thereof comprises: a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:9, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:10; or a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:29, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:30.

[0235] Embodiment 36. A lyophilized preparation, wherein the lyophilized preparation is obtained by freeze-drying the pharmaceutical composition according to any one of Embodiments 1-35; or the lyophilized preparation can form the pharmaceutical composition according to any one of Embodiments 1-35 after reconstitution.

[0236] Embodiment 37. A vial, wherein the vial contains the pharmaceutical composition of any one of Embodiments 1-35 or the lyophilized formulation of Embodiment 36.

[0237] Embodiment 38. Use of the pharmaceutical composition of any one of Embodiments 1-35 or the lyophilized formulation of Embodiment 36 in the preparation of a medicament for treating a disease in a subject.

[0238] Embodiment 39. The use according to embodiment 38, wherein the disease comprises cancer and an infectious disease.

[0239] Embodiment 40. The use according to embodiment 39, wherein the cancer is recurrent, refractory, metastatic and / or advanced cancer.

[0240] Embodiment 41. The use according to embodiment 39 or 40, wherein the cancer comprises head and neck cancer, nasopharyngeal cancer, oral cancer, esophageal cancer, lung cancer, liver cancer, colon cancer, colorectal cancer, kidney cancer, endometrial cancer, cervical cancer, glioblastoma, bladder cancer, breast cancer, ovarian cancer, fallopian tube cancer, prostate cancer, anal cancer, testicular cancer, vaginal cancer, gastric cancer, gastroesophageal junction cancer, pancreatic cancer, bone cancer, thyroid cancer, skin cancer, nervous system tumors, sarcoma, myeloma, bile duct cancer, gallbladder cancer, soft tissue sarcoma, lymphoma and hematological tumors.

[0241] Embodiment 42. The use according to any one of embodiments 38-41, wherein the pharmaceutical composition or lyophilized formulation is suitable for parenteral administration.

[0242] The present disclosure is further illustrated by the following examples, which should not be construed as further limiting.The contents of all references, Genbank records, patents, and published patent applications cited in this disclosure are expressly incorporated herein by reference. Example

[0243] The heavy chain amino acid sequence of the anti-LAG-3 antibody in the Examples is shown in SEQ ID NO: 9, and the light chain amino acid sequence is shown in SEQ ID NO: 10. The heavy chain amino acid sequence of the anti-PD-1 antibody in the Examples is shown in SEQ ID NO: 19, and the light chain amino acid sequence is shown in SEQ ID NO: 20.

[0244] Example 1 Preparation of buffer

[0245] Acetic acid-sodium acetate buffer: prepared from acetic acid and sodium acetate trihydrate. For example, 20 mM acetic acid-sodium acetate buffer (pH 6.0) can be prepared from about 2.60 g / L sodium acetate trihydrate and about 0.15 g / L acetic acid (37%).

[0246] Histidine-HCl buffer: prepared with L-histidine and adjusted to the target pH with hydrochloric acid. For example, 20 mM histidine-HCl buffer (pH 5.8) can be prepared with about 3.1 g / L L-histidine and adjusted to pH 5.8 with hydrochloric acid.

[0247] Histidine-acetate buffer: prepared with L-histidine and adjusted to the target pH with acetic acid. For example, 20 mM histidine-acetate buffer (pH 5.8) can be prepared with about 3.1 g / L L-histidine and adjusted to pH 5.8 with acetic acid.

[0248] Example 2 Detection Method of Pharmaceutical Composition

[0249] Size exclusion chromatography (SEC-UPLC): Thermo Vanquish F high-performance liquid chromatography, Waters ACQUITY UPLC Protein BEH SEC Column Gel chromatography column, Waters ACQUITY UPLC Protein BEH SEC Guard Column The column was pre-eluted with 50 mmol / L phosphate buffer-200 mmol / L sodium chloride solution (pH 7.0) as the mobile phase and the detection wavelength was 280 nm. The peak area percentages of the high molecular weight impurities and the main peak were calculated by area normalization method.

[0250] Size exclusion chromatography (SEC-HPLC): Thermo high performance liquid chromatograph, TOSOH, TSKgel G3000 SW XL (7.8 mm × 30 cm, 5 μm) chromatographic column, TOSOH, TSKgel G3000 guardcolumn SW XL A pre-column (6 mm × 4 cm, 7 μm) was used and eluted with 50 mmol / L phosphate buffer-300 mmol / L sodium chloride-200 mmol / L arginine hydrochloride (pH 7.0) as the mobile phase. The components were eluted in descending order of molecular weight and detected at a wavelength of 280 nm. The peak area percentages of high molecular weight impurities and the main peak were calculated using the area normalization method.

[0251] Nonreducing sodium dodecyl sulfate capillary electrophoresis (nonreducing CE-SDS) was performed using a Beckman Coulter PA 800 Plus Biopharmaceutical Analysis System, uncoated fused silica capillaries (50 μm inner diameter), and a PDA detector at a wavelength of 220 nm. The corrected peak area percentages of the main peak and low-molecular-weight impurities were calculated by area normalization.

[0252] Unfolding temperature (Tm): A protein stability analyzer (NanoTemper, Prometheus NT.48) was used to analyze the unfolding temperature (Tm) of the sample. 10 μL of sample was taken into the sample chamber using a capillary tube. The program was as follows: the scan start temperature was 25°C, the scan end temperature was 95°C, and the heating rate was 0.3°C / min.

[0253] Aggregation temperature (Tagg): A multi-well plate direct-reading dynamic and static light scattering instrument (Wyatt, Dynaproplate Reader III) was used to analyze the aggregation temperature (Tagg) of the samples. After the samples were centrifuged, 30 μL of the supernatant was added to a 384-well sample plate. The plate was sealed with a sealing film, and the 384-well sample plate was centrifuged to remove bubbles. The test was then performed using the following procedure: the temperature was raised from 25°C to 85°C, and the scan time was 5 seconds.

[0254] Particle size: The particle size of the samples was measured using a nanoparticle size analyzer (Malvern, ZEN3600) with the following procedure: temperature 25°C, equilibration time 120 s.

[0255] Example 3 Screening of pharmaceutical compositions

[0256] The anti-LAG-3 antibody was replaced by ultrafiltration into the buffer listed in Table 3-1. After the replacement, the solution was concentrated, and then a surfactant and stabilizer were added according to Table 3-1 to obtain an anti-LAG-3 antibody stock solution. The anti-PD-1 antibody stock solution was prepared in the same manner. The anti-LAG-3 antibody stock solution and the anti-PD-1 antibody stock solution were mixed uniformly in proportion to obtain pharmaceutical compositions Fa1-Fa6, wherein the concentration of the anti-LAG-3 antibody was 4 mg / mL and the concentration of the anti-PD-1 antibody was 12 mg / mL. The pharmaceutical compositions were sterilized by filtration through a 0.22 μm filter membrane and dispensed into vials, stoppered, and capped.

[0257] The pharmaceutical compositions shown in Table 3-1 were subjected to Tm and Tagg assays. The test results are shown in Table 3-2. These results demonstrate good conformational and colloidal stability of the antibodies within the pH range of 5.0-7.0. The pharmaceutical compositions shown in Table 3-1 were stored at 40°C for one and two weeks, respectively. The SEC-UPLC assay results are shown in Table 3-3.

[0258] Table 3-1. Components of the pharmaceutical composition

[0259] Table 3-2. Tm and Tagg test results of pharmaceutical compositions

[0260] Table 3-3. SEC-UPLC test results of pharmaceutical compositions

[0261] Example 4 Screening of pharmaceutical compositions

[0262] The anti-LAG-3 antibody was replaced by ultrafiltration into the buffer listed in Table 4-1. After the replacement, the solution was concentrated, and then a surfactant and stabilizer were added according to Table 4-1 to obtain an anti-LAG-3 antibody stock solution. The anti-PD-1 antibody stock solution was prepared using the same method. The anti-LAG-3 antibody stock solution and the anti-PD-1 antibody stock solution were mixed uniformly in proportion to obtain pharmaceutical compositions Fb1-Fb6, wherein the concentration of the anti-LAG-3 antibody was 15 mg / mL and the concentration of the anti-PD-1 antibody was 5 mg / mL. The pharmaceutical composition was sterilized by filtration through a 0.22 μm filter membrane and dispensed into vials, stoppered, and capped.

[0263] The pharmaceutical composition shown in Table 4-1 was subjected to Tm and Tagg testing. The test results are shown in Table 4-2. The results show that the antibody has good conformational stability and colloidal stability in the pH range of 5.0-6.3. The pharmaceutical composition shown in Table 4-1 was placed at 40°C and 2-8°C, respectively. The results of SEC-HPLC and non-reducing CE-SDS testing are shown in Table 4-3. The results show that 80-164.3 mg / mL sucrose has a good effect on maintaining antibody stability.

[0264] Table 4-1. Components of the pharmaceutical composition

[0265] Table 4-2. Tm and Tagg test results of pharmaceutical compositions

[0266] Table 4-3. SEC-HPLC and non-reduced CE-SDS detection results of pharmaceutical compositions

[0267] Example 5 Screening of pharmaceutical compositions

[0268] The anti-LAG-3 antibody was replaced by ultrafiltration into the buffer listed in Table 5-1. After the replacement, the solution was concentrated, and then a surfactant and stabilizer were added according to Table 5-1 to obtain an anti-LAG-3 antibody stock solution. An anti-PD-1 antibody stock solution was prepared using the same method. The anti-LAG-3 antibody stock solution and the anti-PD-1 antibody stock solution were mixed uniformly in proportion to obtain a pharmaceutical composition Fc1-Fc5, wherein the concentration of the anti-LAG-3 antibody was 15 mg / mL and the concentration of the anti-PD-1 antibody was 5 mg / mL. The pharmaceutical composition was sterilized by filtration through a 0.22 μm filter membrane and dispensed into vials, stoppered, and capped.

[0269] The pharmaceutical composition shown in Table 5-1 was subjected to Tm and Tagg tests, and the test results are shown in Table 5-2. The pharmaceutical composition shown in Table 5-1 was placed at 40°C and 2-8°C, respectively, and the results of SEC-HPLC and non-reducing CE-SDS tests are shown in Table 5-3. The results show that histidine-acetate buffer is superior to acetic acid-sodium acetate buffer.

[0270] Table 5-1. Components of the pharmaceutical composition

[0271] Table 5-2. Tm and Tagg test results of pharmaceutical compositions

[0272] Table 5-3. SEC-HPLC and non-reduced CE-SDS test results of pharmaceutical compositions

[0273] Example 6 Screening of pharmaceutical compositions

[0274] The anti-LAG-3 antibody was replaced by ultrafiltration into the buffer listed in Table 6-1. After the replacement, the solution was concentrated, and then a surfactant and stabilizer were added according to Table 6-1 to obtain an anti-LAG-3 antibody stock solution. The anti-PD-1 antibody stock solution was prepared using the same method. The anti-LAG-3 antibody stock solution and the anti-PD-1 antibody stock solution were mixed uniformly in proportion to obtain pharmaceutical compositions Fd1 and Fd2, wherein the concentration of the anti-LAG-3 antibody was 15 mg / mL and the concentration of the anti-PD-1 antibody was 5 mg / mL. The pharmaceutical compositions were sterilized by filtration through a 0.22 μm filter membrane and dispensed into vials, stoppered, and capped.

[0275] The pharmaceutical composition shown in Table 6-1 was subjected to Tm and Tagg tests, and the test results are shown in Table 6-2. The pharmaceutical composition shown in Table 6-1 was placed at 40°C and 2-8°C, respectively, and the particle size and SEC-HPLC test results are shown in Table 6-3.

[0276] Table 6-1. Components of the pharmaceutical composition

[0277] Table 6-2. Tm and Tagg test results of pharmaceutical compositions

[0278] Table 6-3. Particle size and SEC-HPLC test results of the pharmaceutical composition

[0279] Example 7 Screening of pharmaceutical compositions

[0280] The anti-LAG-3 antibody was replaced by ultrafiltration into the buffer listed in Table 7-1. After the replacement, the solution was concentrated, and then a surfactant and stabilizer were added according to Table 7-1 to obtain an anti-LAG-3 antibody stock solution. The anti-PD-1 antibody stock solution was prepared in the same manner. The anti-LAG-3 antibody stock solution and the anti-PD-1 antibody stock solution were mixed uniformly in proportion to obtain a pharmaceutical composition Fe1, wherein the concentration of the anti-LAG-3 antibody was 15 mg / mL and the concentration of the anti-PD-1 antibody was 5 mg / mL. The pharmaceutical composition was sterilized by filtration through a 0.22 μm filter membrane and dispensed into vials, stoppered, and capped.

[0281] The pharmaceutical composition shown in Table 7-1 was placed at 40°C, 25°C and 2-8°C, respectively. The particle size and SEC-HPLC test results are shown in Table 7-2.

[0282] Table 7-1. Components of the pharmaceutical composition

[0283] Table 7-2. Particle size and SEC-HPLC test results of the pharmaceutical composition

Claims

1. A pharmaceutical composition comprising (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) a buffer, (c) one or more stabilizers, and (d) a surfactant, wherein: The anti-PD-1 antibody or antigen-binding fragment thereof comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 11, HCDR2 of the amino acid sequence shown in SEQ ID NO: 12, HCDR3 of the amino acid sequence shown in SEQ ID NO: 13, LCDR1 of the amino acid sequence shown in SEQ ID NO: 14, LCDR2 of the amino acid sequence shown in SEQ ID NO: 15, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 16; The anti-LAG-3 antibody or antigen-binding fragment thereof comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO:1, HCDR2 of the amino acid sequence shown in SEQ ID NO:2, HCDR3 of the amino acid sequence shown in SEQ ID NO:3, LCDR1 of the amino acid sequence shown in SEQ ID NO:4, LCDR2 of the amino acid sequence shown in SEQ ID NO:5, and LCDR3 of the amino acid sequence shown in SEQ ID NO:6; or HCDR1 of the amino acid sequence shown in SEQ ID NO:21, HCDR2 of the amino acid sequence shown in SEQ ID NO:22, HCDR3 of the amino acid sequence shown in SEQ ID NO:23, LCDR1 of the amino acid sequence shown in SEQ ID NO:24, LCDR2 of the amino acid sequence shown in SEQ ID NO:25, and LCDR3 of the amino acid sequence shown in SEQ ID NO:

26.

2. The pharmaceutical composition according to claim 1, wherein The anti-PD-1 antibody or antigen-binding fragment thereof and the anti-LAG-3 antibody or antigen-binding fragment thereof are present in the pharmaceutical composition at a fixed dose ratio, wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:1-9, 1:1-8, 1:1-6, 1:1-5, 1:1-4.5, 1:1-4, 1:1-3.5, 1:1-3, 1:1-2.5, 1:1-2, 1:1-1.5, 1:1-1.25, 1:0.1-1, 1:0.4-1 or 1:0.8-1; Optionally, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 1-100 mg / mL, 1-80 mg / mL, 2-60 mg / mL, 3-30 mg / mL, 4-20 mg / mL, 5-20 mg / mL, 5-15 mg / mL, or 5-10 mg / mL; and / or the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 1-200 mg / mL, 2-160 mg / mL, 3-120 mg / mL, 4-80 mg / mL, 5-50 mg / mL, 5-40 mg / mL, 5-30 mg / mL, 5-20 mg / mL, or 5-15 mg / mL.

3. The pharmaceutical composition according to claim 1 or 2, wherein The buffer comprises histidine buffer, acetate buffer, Tris buffer, phosphate buffer or citrate buffer; Optionally, the concentration of the buffer is 1-100 mM, 2-80 mM, 5-60 mM, 10-40 mM, or 10-20 mM.

4. The pharmaceutical composition according to any one of claims 1 to 3, wherein The pharmaceutical composition comprises 1-100 mM, 2-80 mM, 5-60 mM, 10-40 mM, or 10-20 mM histidine buffer.

5. The pharmaceutical composition according to any one of claims 1 to 4, wherein The stabilizer comprises mannitol, sorbitol, trehalose, sucrose, maltose, lactose, lysine, glycine, proline, arginine or a pharmaceutically acceptable salt thereof, or sodium chloride; preferably, the stabilizer comprises sucrose, proline, or arginine or a pharmaceutically acceptable salt thereof.

6. The pharmaceutical composition according to any one of claims 1 to 5, wherein The pharmaceutical composition comprises 1-400 mg / mL, 10-300 mg / mL, 20-200 mg / mL, 40-200 mg / mL, 40-180 mg / mL, 60-180 mg / mL, or 70-170 mg / mL of sucrose; and / or 10-1000 mM, 50-800 mM, 100-700 mM, 100-600 mM, 150-600 mM, 200-600 mM, 200-500 mM, or 200-300 mM proline.

7. The pharmaceutical composition according to any one of claims 1 to 6, wherein The surfactant comprises polysorbate 80 or polysorbate 20; Optionally, the concentration of the surfactant is 0.01-3 mg / mL, 0.04-2 mg / mL, 0.08-1.6 mg / mL, 0.1-1.2 mg / mL, 0.1-1 mg / mL, 0.2-0.8 mg / mL, or 0.4-0.8 mg / mL.

8. The pharmaceutical composition according to any one of claims 1 to 7, wherein The pharmaceutical composition comprises 0.01-3 mg / mL, 0.04-2 mg / mL, 0.08-1.6 mg / mL, 0.1-1.2 mg / mL, 0.1-1 mg / mL, 0.2-0.8 mg / mL, or 0.4-0.8 mg / mL of polysorbate 80.

9. The pharmaceutical composition according to any one of claims 1 to 8, wherein The pH of the pharmaceutical composition is 5 to 7, 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3 to 6.2, 5.3 to 6, 5.5 to 6, 5.3 to 5.8, or 5.5 to 5.

8.

10. The pharmaceutical composition according to any one of claims 1 to 9, wherein The pharmaceutical composition comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 1-100 mM histidine buffer, (c) 1-400 mg / mL sucrose and 10-1000 mM proline, and (d) 0.01-3 mg / mL polysorbate 80 or polysorbate 20; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4, and the pH of the pharmaceutical composition is 5 to 6.3; (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) a 10-20 mM histidine buffer, (c) 60-180 mg / mL sucrose and 200-500 mM proline, and (d) 0.4-0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3; (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer, (c) 80-164.3 mg / mL sucrose and 200-300 mM proline, and (d) 0.4-0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or an antigen-binding fragment thereof to the anti-LAG-3 antibody or an antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3; (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer, (c) 80-164.3 mg / mL sucrose and 200-300 mM proline, and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or an antigen-binding fragment thereof to the anti-LAG-3 antibody or an antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3; (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer, (c) 80-160 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or an antigen-binding fragment thereof to the anti-LAG-3 antibody or an antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3; (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer, (c) 108.1 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or an antigen-binding fragment thereof to the anti-LAG-3 antibody or an antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3; (a) 1-100 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 1-200 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 1-100 mM histidine buffer, (c) 1-400 mg / mL sucrose and 10-1000 mM proline, and (d) 0.01-3 mg / mL polysorbate 80 or polysorbate 20; and the pH of the pharmaceutical composition is 5 to 6.3; (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer, (c) 60-180 mg / mL sucrose and 200-500 mM proline, and (d) 0.4-0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5 to 6.3; (a) 5-10 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 5-30 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer, (c) 80-164.3 mg / mL sucrose and 200-300 mM proline, and (d) 0.4-0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5 to 6.3; (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer, (c) 80-164.3 mg / mL sucrose and 200-300 mM proline, and (d) 0.8 mg / mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-LAG-3 antibody or antigen-binding fragment thereof is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3; (a) 5 mg / mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer, (c) 80-160 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5 to 6.3; or (a) 5 mg / mL anti-PD-1 antibody or an antigen-binding fragment thereof and 15 mg / mL anti-LAG-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer, (c) 108.1 mg / mL sucrose and 200 mM proline, and (d) 0.8 mg / mL polysorbate 80; and the pH of the pharmaceutical composition is 5 to 6.

3.

11. The pharmaceutical composition according to any one of claims 1 to 10, wherein The anti-PD-1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 17, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 18; Optionally, the anti-PD-1 antibody or antigen-binding fragment thereof comprises: a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 19, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:

20.

12. The pharmaceutical composition according to any one of claims 1 to 11, wherein The anti-LAG-3 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:8; or a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:27, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:28; Optionally, the anti-LAG-3 antibody or antigen-binding fragment thereof comprises: a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:9, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:10; or a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:29, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:

30.

13. A freeze-dried preparation, wherein: The lyophilized preparation is obtained by freeze-drying the pharmaceutical composition according to any one of claims 1 to 12; or the lyophilized preparation can form the pharmaceutical composition according to any one of claims 1 to 12 after being reconstituted.

14. A vial, wherein: The vial contains the pharmaceutical composition according to any one of claims 1 to 12 or the lyophilized preparation according to claim 13.

15. Use of the pharmaceutical composition according to any one of claims 1 to 12 or the lyophilized preparation according to claim 13 in the preparation of a medicament for treating a disease in a subject; Optionally, the disease includes cancer and infectious disease; Optionally, the cancer is recurrent, refractory, metastatic and / or advanced cancer; Optionally, the cancer includes head and neck cancer, nasopharyngeal cancer, oral cancer, esophageal cancer, lung cancer, liver cancer, colon cancer, colorectal cancer, kidney cancer, endometrial cancer, cervical cancer, glioblastoma, bladder cancer, breast cancer, ovarian cancer, fallopian tube cancer, prostate cancer, anal cancer, testicular cancer, vaginal cancer, gastric cancer, gastroesophageal junction cancer, pancreatic cancer, bone cancer, thyroid cancer, skin cancer, nervous system tumors, sarcoma, myeloma, bile duct cancer, gallbladder cancer, soft tissue sarcoma, lymphoma and hematological tumors.