[go: up one dir, main page]

WO2025056011A1 - Composition pharmaceutique comprenant un anticorps anti-pd-1 et un second anticorps - Google Patents

Composition pharmaceutique comprenant un anticorps anti-pd-1 et un second anticorps Download PDF

Info

Publication number
WO2025056011A1
WO2025056011A1 PCT/CN2024/118665 CN2024118665W WO2025056011A1 WO 2025056011 A1 WO2025056011 A1 WO 2025056011A1 CN 2024118665 W CN2024118665 W CN 2024118665W WO 2025056011 A1 WO2025056011 A1 WO 2025056011A1
Authority
WO
WIPO (PCT)
Prior art keywords
antibody
antigen
binding fragment
pharmaceutical composition
lag
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/CN2024/118665
Other languages
English (en)
Chinese (zh)
Inventor
孔令婕
李盈淳
程艳菊
焦梦莹
刘成军
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chia Tai Tianqing Pharmaceutical Guangzhou Co Ltd
Chia Tai Tianqing Pharmaceutical Group Co Ltd
Original Assignee
Chia Tai Tianqing Pharmaceutical Guangzhou Co Ltd
Chia Tai Tianqing Pharmaceutical Group Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chia Tai Tianqing Pharmaceutical Guangzhou Co Ltd, Chia Tai Tianqing Pharmaceutical Group Co Ltd filed Critical Chia Tai Tianqing Pharmaceutical Guangzhou Co Ltd
Publication of WO2025056011A1 publication Critical patent/WO2025056011A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7016—Disaccharides, e.g. lactose, lactulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Definitions

  • 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.
  • PD-1 Programmed death-1 is mainly expressed by activated T lymphocytes and B lymphocytes, and its ligands include PD-L1 and PD-L2.
  • the binding of PD-1 to its ligand will inhibit T cell activation and proliferation, downregulate the secretion of T cell immunostimulatory cytokines, thereby inhibiting T cell immune response and promoting T cell apoptosis.
  • PD-1 is highly expressed on tumor-infiltrating lymphocytes, and its ligand is also upregulated on the surface of a variety of tumor cells. Therefore, anti-PD-1 antibodies can block the immunosuppressive signaling pathway and enhance the body's endogenous anti-tumor immune effect by blocking the binding of PD-1 to its ligand.
  • Lymphocyte activation gene-3 belongs to the immunoglobulin superfamily and is mainly expressed on the surface of activated T cells, NK cells, B cells, plasmacytoid dendritic cells and other cells.
  • LAG-3 has a variety of different ligands, including major histocompatibility complex-II molecule (MHC-II), fibronectin protein 1 (FGL1), galectin-3 and liver sinusoidal endothelial cell lectin (LSECtin). LAG-3 can negatively regulate T cells and play an important role in maintaining the homeostasis of the body's immune system.
  • MHC-II major histocompatibility complex-II
  • FGL1 fibronectin protein 1
  • LSECtin liver sinusoidal endothelial cell lectin
  • tumor cells highly express LAG-3 ligands, which bind to LAG-3 highly expressed on tumor infiltrating lymphocytes (TILs), leading to T cell dysfunction or even exhaustion, aggravating tumor cell immune escape and promoting tumor development.
  • TILs tumor infiltrating lymphocytes
  • Anti-PD-1 antibodies can be administered in combination with anti-LAG-3 antibodies, but administration of the two antibodies requires multiple doses at different time points, so a single formulation containing both antibodies will improve patient convenience and reduce drug resistance. Because each antibody has unique physical and chemical properties, such as surface exposed residues, breakable sites, glycosylation 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.
  • 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.
  • the second antibody or an antigen-binding fragment thereof is an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the anti-PD-1 antibody or an antigen-binding fragment thereof and the anti-LAG-3 antibody or an antigen-binding fragment thereof are present in the pharmaceutical composition at a fixed dose ratio.
  • 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 1:1-15, 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.
  • the present disclosure also provides a lyophilized preparation, wherein the lyophilized preparation is obtained by freeze-drying the pharmaceutical composition of the present disclosure.
  • the present disclosure also provides a lyophilized preparation, wherein the lyophilized preparation can form the pharmaceutical composition of the present disclosure after reconstitution.
  • 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.
  • 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.
  • the present disclosure also provides a method for preparing the pharmaceutical composition and lyophilized preparation of the present disclosure.
  • 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.
  • the disease includes cancer and infectious diseases.
  • the present disclosure also provides a method for enhancing an immune response 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.
  • buffer means a pharmaceutically acceptable buffer, which refers to a substance that helps maintain the pH of the pharmaceutical composition within a desired pH range.
  • Buffers suitable for use in the present disclosure include phosphate buffers, acetate buffers, citrate buffers, Tris buffers, or histidine buffers. In addition, a mixture of two or more buffers may also be used.
  • phosphate buffer is a buffer containing phosphate ions.
  • 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).
  • acetate buffer is a buffer containing acetate ions.
  • acetate buffers include potassium acetate buffer, ammonium acetate buffer, sodium acetate buffer, etc.
  • 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).
  • citrate buffer is a buffer containing citrate ions.
  • examples of citrate buffers include sodium citrate buffer, potassium citrate buffer, calcium citrate buffer, etc.
  • Sodium citrate buffer can be prepared using citric acid and sodium citrate or a hydrate thereof (e.g., trisodium citrate dihydrate).
  • histidine buffer is a buffer comprising histidine ions.
  • 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 its hydrate (e.g., monohydrated histidine hydrochloride).
  • Histidine-hydrochloride buffer can be prepared using histidine (e.g., L-histidine), and the pH is further adjusted with hydrochloric acid.
  • Histidine-acetate buffer can be prepared using histidine (e.g., L-histidine), and the pH is further adjusted with acetic acid.
  • Histidine-phosphate buffer can be prepared using histidine (e.g., L-histidine), and the pH is further adjusted with phosphoric acid.
  • stabilizer refers to a substance that helps maintain the structural integrity of an active ingredient (e.g., an antibody) in a pharmaceutical composition, particularly during freezing, lyophilization, storage and/or transportation (especially when exposed to stress).
  • a stabilizer may also function as a viscosity reducer, an antioxidant and/or an isotonic agent.
  • antioxidant refers to a substance that can prevent or reduce oxidation of an active ingredient (eg, an antibody) in a pharmaceutical composition.
  • isotonic agent refers to a substance that helps maintain the osmotic pressure of a pharmaceutical composition at or close to the physiological osmotic pressure.
  • excipient refers to any ingredient other than the active ingredient.
  • 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.
  • pharmaceutically acceptable excipients include, but are not limited to, excipients, diluents, fillers, binders, chelating agents, disintegrants, solubilizers, stabilizers, colorants, flavoring agents, surfactants, emulsifiers, buffers, or encapsulating materials.
  • stable pharmaceutical composition refers to a pharmaceutical composition in which the active ingredient (e.g., an antibody) substantially retains its physical stability and/or chemical stability and/or biological activity when stored therein.
  • active ingredient e.g., an antibody
  • Stability can be measured at a selected temperature and other storage conditions for a selected time period.
  • an active ingredient "retains its physical stability” in a pharmaceutical composition if it does not show significant increase in aggregation, precipitation and/or denaturation as measured by visual inspection of color and/or clarity, or by UV light scattering, size exclusion chromatography (SEC) and differential scanning calorimetry (DSC).
  • An active ingredient e.g., an antibody
  • 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 electrophoresis, peptide mapping, isoaspartate measurement) and isomerization (which can be assessed by measuring isoaspartate content, peptide mapping, etc.).
  • 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 electrophoresis, peptid
  • An active ingredient e.g., an antibody "retains its biological activity" over a given period of time in a pharmaceutical composition if the biological activity of the active ingredient over a given period of time is within a predetermined range of the biological activity exhibited when the pharmaceutical composition is prepared, which can be determined by an antigen binding assay.
  • 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).
  • the term "antibody” refers to an antigen binding protein having at least one antigen binding domain.
  • the antibody or fragment thereof of the present disclosure 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 the antibody or antigen binding fragment thereof of the present disclosure 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.
  • the "antibody or its antigen-binding fragment” disclosed herein includes the whole antibody and any antigen-binding fragment or single chain thereof.
  • 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 consists of one domain CL.
  • the VH and VL regions can also be divided into hypervariable regions, i.e., complementary determining regions (CDRs), and framework regions (FRs) with relatively conservative sequences.
  • 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 the antibody contains a binding domain that interacts with the antigen.
  • the constant region of the antibody can mediate the binding of the 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.
  • special "whole antibodies" such as nanobodies, have only heavy (H) chains and no light (L) chains.
  • the "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 a fragment of the entire antibody. Examples encompassed in the "antigen-binding fragment” of an antibody include: (i) Fab fragment: a monovalent fragment consisting of VL, VH, CL, and CH1 domains; (ii) F(ab') 2 fragment, a bivalent fragment comprising two Fab fragments connected by a disulfide bridge in the hinge region; (iii) Fd fragment consisting of VH and CH1 domains; (iv) Fv fragment consisting of the VL and VH domains of a single antibody arm; (v) dAb fragment consisting of a VH domain (see Ward et al., Nature.
  • VH and VL can be connected into a single protein chain by a recombinant method through a synthetic linker, wherein VL and VH are paired 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)).
  • scFv single-chain Fv
  • antigen-binding fragment single-chain antibodies are also encompassed in the term antigen-binding fragment.
  • recombinant polypeptides, fusion proteins and immunoconjugates comprising the antigen-binding fragment are also encompassed in the term antigen-binding fragment.
  • 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.
  • a chimeric antibody may comprise a murine variable region and a human constant region.
  • a “humanized antibody” is an antibody that contains complementary determining regions (CDRs) derived from a non-human antibody and framework and constant regions derived from a human antibody.
  • CDRs complementary determining regions
  • an anti-LAG-3 antibody and an anti-PD-1 antibody may contain CDRs derived from one or more murine antibodies and human framework and human constant regions.
  • Additional anti-LAG-3 antibodies or variants thereof comprising the HCDRs and LCDRs provided herein may be generated using any human framework sequence and are also included in the present disclosure.
  • Additional anti-PD-1 antibodies or variants thereof comprising the HCDRs and LCDRs provided herein may be generated using any human framework sequence and are also included in the present disclosure.
  • 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 compared that are identical to the amino acid residues in the specific amino acid sequence shown in this article, after comparing the sequence to be compared with the specific amino acid sequence shown in this article and introducing spaces if necessary to achieve the maximum sequence identity percentage, and not considering any conservative substitutions as part of the sequence identity.
  • the amino acid sequence alignment of identity can be carried out 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 comparing sequences, including any algorithm required to obtain the maximum alignment in the full length of the comparison sequence.
  • fixed dose ratio refers to two or more different antibodies or antigen-binding fragments thereof in a single pharmaceutical composition that are present in a specific (fixed) ratio relative to each other in the pharmaceutical composition, and the ratio is the fixed dose ratio.
  • the fixed dose ratio is based on the mass (e.g., mg) of the antibody or antigen-binding fragment thereof.
  • the fixed dose ratio is based on the concentration (e.g., mg/mL) of the antibody or antigen-binding fragment thereof.
  • multiples/fractions refer to multiples or fractions of a parameter/value.
  • 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).
  • treatment generally refers to an operation to obtain a desired pharmacological and/or physiological effect.
  • the effect may 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.
  • treatment encompasses any treatment of a patient's disease, including but not limited to preventing the occurrence or recurrence of a disease, alleviating symptoms of a disease, reducing any direct or indirect pathological consequences of a disease, preventing the metastasis of a disease, slowing the progression of a disease, ameliorating or alleviating the symptoms of a disease, state, prolong the frequency and duration of symptom-free period, and resolve or improve the prognosis of the disease.
  • “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 regression of disease, 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 caused by 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.
  • administering refers 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.
  • the terms “subject”, “patient” or “subject” are used interchangeably.
  • “Subject”, “patient” or “subject” includes any person 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 (such as mice, rats and guinea pigs).
  • the subject, patient or subject is a mammal.
  • the subject, patient or subject is a mouse.
  • the subject, patient or subject is a human.
  • a pharmaceutical composition refers to one pharmaceutical composition or more than one pharmaceutical composition.
  • “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., the limitations of the measurement system. For example, “about” may mean within 1 or more than 1 standard deviation as practiced in the art. Alternatively, “about” may mean a range of up to ⁇ 5%, such as fluctuations within ⁇ 2%, within ⁇ 1%, or within ⁇ 0.5% of a given specific numerical range. When specific values or parameters are given herein or in the claims, they are modified by “about” by default unless otherwise indicated.
  • the words “comprise”, “include” and “contain” will be understood to mean including the stated 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 necessary, 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 necessary, but other elements are optional and may be present or absent depending on whether they affect the activity or action of the listed elements.
  • any numerical range e.g., concentration range, percentage range, or ratio range
  • any integer value within the range, and where appropriate, fractions thereof (such as tenths and hundredths of integers), unless otherwise specified.
  • 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.
  • the second antibody or an antigen-binding fragment thereof is an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • a pharmaceutical composition when two or more antibodies or antigen-binding fragments thereof are included in a "pharmaceutical composition", the two or more antibodies or antigen-binding fragments thereof are formulated together and stored in a single vial or container (e.g., injection device) as a combined product, 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 production and/or administration to a patient, and to maintain biological activity and/or stability during storage and subsequent use.
  • the pharmaceutical composition of the present disclosure is an injection.
  • the injection includes but is not limited to a non-lyophilized water-soluble preparation or a water-soluble preparation reconstituted from a lyophilized preparation.
  • 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.
  • 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.
  • 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • 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 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.
  • 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 in the pharmaceutical composition is 1.25:1, 1:1, 1:1.5, 1:2, 1:3 or 1:4.
  • 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 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment in the pharmaceutical composition is 1:3.
  • 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.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, such as 100 mg, or 200 mg, or multiples/fractions thereof. In some embodiments, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg. In some embodiments, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg.
  • 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, such as 40 mg, 80 mg, 120 mg, 160 mg, 200 mg, 240 mg, 280 mg, 300 mg, 320 mg.
  • the anti-LAG-3 antibody or antigen-binding fragment thereof has a mass of 300 mg or 600 mg.
  • the anti-LAG-3 antibody or antigen-binding fragment thereof has a mass of 300 mg or 600 mg.
  • the anti-LAG-3 antibody or antigen-binding fragment thereof has a mass of 300 mg or 600 mg.
  • the anti-LAG-3 antibody or antigen-binding fragment thereof has a mass of 300 mg or 600 mg.
  • 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.
  • the pharmaceutical composition comprises 100 mg, or 200 mg, or multiples/fractions thereof of an anti-PD-1 antibody or an 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/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the pharmaceutical composition comprises 100 mg, 200 mg, or multiples/fractions thereof of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 200 mg, or multiples/fractions thereof of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 160 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the pharmaceutical composition comprises 200 mg, or multiples/fractions thereof of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 300 mg, 400 mg, or 600 mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the pharmaceutical composition comprises 100 mg or 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 300 mg or 600 mg of an anti-LAG-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 600 mg of an anti-LAG-3 antibody or an 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.
  • 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.
  • 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment 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 a range formed by any value.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4 mg/mL. In some embodiments, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL. In some embodiments, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 8 mg/mL. In some embodiments, the anti-PD-1 antibody In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 15 mg/mL.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 an 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 an antigen-binding fragment thereof.
  • the present invention relates to an anti-LAG-3 antibody or an antigen-binding fragment thereof at a concentration of 1 mg/mL, 2 mg/mL, 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 of an anti-LAG-3 antibody or an antigen-binding
  • 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.
  • 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.
  • 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.
  • compositions of the present disclosure may further comprise one or more pharmaceutically acceptable excipients, such as buffers, stabilizers, diluents, chelating agents, and surfactants.
  • pharmaceutically acceptable excipients such as buffers, stabilizers, diluents, chelating agents, and surfactants.
  • the pharmaceutical composition of the present disclosure further comprises one or more buffers.
  • the buffer comprises a histidine buffer, an acetate buffer, a Tris buffer, a phosphate buffer, or a citrate buffer.
  • the buffer comprises a histidine buffer or an acetate buffer.
  • the buffer comprises a histidine buffer.
  • the buffer comprises an acetate buffer.
  • the histidine buffer may be a histidine-histidine hydrochloride buffer, a histidine-hydrochloride buffer, a histidine-acetate buffer, or a histidine-phosphate buffer.
  • the histidine buffer may be a histidine-acetate buffer.
  • the acetate buffer can be a sodium acetate buffer, a potassium acetate buffer, or an ammonium acetate buffer.
  • the acetate buffer can be a sodium acetate buffer.
  • the phosphate buffer can be a sodium phosphate buffer or a potassium phosphate buffer.
  • the citrate buffer can be a sodium citrate buffer, a potassium citrate buffer, or a calcium citrate buffer.
  • the concentration of the buffer is 1-100mM, 2-80mM, 5-60mM, 10-40mM, or 10-20mM. In some embodiments, the concentration of the buffer includes but is not limited to: 5mM, 10mM, 11mM, 12mM, 13mM, 14mM, 15mM, 16mM, 17mM, 18mM, 19mM, 20mM, 21mM, 22mM, 23mM, 24mM, 25mM, 26mM, 27mM, 28mM, 29mM, 30mM, 32mM, 34mM, 36mM, 38mM, 40mM, 50mM, or 60mM, or a range formed by any value.
  • the concentration of the buffer is 10mM. In some embodiments, the concentration of the buffer is 20mM. 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.
  • 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.
  • 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.
  • the pH of the buffer is 5.
  • the pH of the buffer is 5.3.
  • the pH of the buffer is 5.5.
  • 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.
  • the pharmaceutical composition of the present disclosure also includes one or more stabilizers.
  • the stabilizer is selected from sugar alcohols (e.g., mannitol, sorbitol), disaccharides (e.g., trehalose, sucrose, maltose, lactose), monosaccharides (e.g., dextrose (D-glucose)), amino acids (e.g., lysine, glycine, proline, arginine or its pharmaceutically acceptable salt), or salts (e.g., sodium chloride).
  • sugar alcohols e.g., mannitol, sorbitol
  • disaccharides e.g., trehalose, sucrose, maltose, lactose
  • monosaccharides e.g., dextrose (D-glucose)
  • amino acids e.g., lysine, glycine, proline, arginine or its pharmaceutically acceptable salt
  • 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.
  • the pharmaceutical composition comprises mannitol, sorbitol, trehalose, sucrose, maltose, lactose, lysine, glycine, proline, arginine or a pharmaceutically acceptable salt thereof, and/or sodium chloride.
  • the pharmaceutical composition comprises mannitol, sorbitol, trehalose, sucrose, proline, arginine or a pharmaceutically acceptable salt thereof, and/or sodium chloride.
  • the pharmaceutical composition comprises sucrose, proline, and/or arginine or a pharmaceutically acceptable salt thereof.
  • the pharmaceutical composition comprises sucrose.
  • the pharmaceutical composition comprises sucrose and proline.
  • the pharmaceutical composition comprises sucrose and arginine or a pharmaceutically acceptable salt thereof.
  • 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.
  • 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 or 300 mg/mL, or a range formed by any value.
  • 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
  • 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.
  • 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.
  • 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.
  • 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, 430m
  • the concentration of the stabilizer is 200-300mM. In some embodiments, the concentration of the stabilizer is 146mM. In some embodiments, the concentration of the stabilizer is 200mM. In some embodiments, the concentration of the stabilizer is 233mM. In some embodiments, the concentration of the stabilizer is 250mM. In some embodiments, the concentration of the stabilizer is 300mM. In some embodiments, the concentration of the stabilizer is 400mM. In some embodiments, the concentration of the stabilizer is 480mM. In some embodiments, the concentration of the stabilizer is 500mM. 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.
  • the pharmaceutical composition of the present disclosure also includes one or more surfactants.
  • the surfactant is a nonionic surfactant.
  • the surfactant includes polysorbate (e.g., polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, polysorbate 81, polysorbate 85), poloxamer (e.g., poloxamer 181, poloxamer 188, poloxamer 407) or polyethylene glycol etc.
  • the surfactant includes polysorbate (e.g., polysorbate 80 or polysorbate 20).
  • the surfactant includes polysorbate 80.
  • 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.
  • the concentration of the surfactant includes but is not limited to: 0.01mg/mL, 0.04mg/mL, 0.06mg/mL, 0.08mg/mL, 0.1mg/mL, 0.15mg/mL, 0.2mg/mL, 0.3mg/mL, 0.4mg/mL, 0.5mg/mL, 0.6mg/mL, 0.7mg/mL, 0.8mg/mL, 0.9mg/mL, 1mg/mL, 1.1mg/mL, 1.2mg/mL, 1.3mg/mL, 1.4mg/mL, 1.5mg/mL, 1.6mg/mL, or 2mg/mL, or a range formed by any value.
  • the concentration of the surfactant is 0.2mg/mL. In some embodiments, the concentration of the surfactant is 0.4mg/mL. In some embodiments, the concentration of the surfactant is 0.5mg/mL. In some embodiments, the concentration of the surfactant is 0.6mg/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.
  • 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.
  • 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 a range formed by any value.
  • the pH of the pharmaceutical composition is 5.
  • the pH of the pharmaceutical composition is 5.3.
  • the pH of the pharmaceutical composition is 5.5.
  • the pH of the pharmaceutical composition is 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.
  • 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 1:1-9, 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)
  • 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 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).
  • 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 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:
  • 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.
  • 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
  • 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of anti-PD-1 antibody or its antigen-binding fragment, and 200 mg, 300 mg, or 400 mg, or multiples/fractions of anti-LAG-3 antibody or its antigen-binding fragment.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • 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 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
  • 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 mixed.
  • mM buffer e.g., acetate buffer or histidine buffer
  • stabilizers e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or
  • 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.
  • 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., sodium acetate buffer, histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and/or arginine or a pharmaceutically acceptable salt 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 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 6.5, 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.
  • mM buffer
  • 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
  • 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of anti-PD-1 antibody or its antigen-binding fragment, and 200 mg, 300 mg, or 400 mg, or multiples/fractions of anti-LAG-3 antibody or its antigen-binding fragment.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • 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 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, 1:1-4.5, 1:1-5, 1:1-6.
  • 2-80 mM buffer e.g., acetate buffer or histidine buffer
  • stabilizers e.g., mann
  • 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 2-80 mM buffer (e.g., an acetate buffer or a histamine 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 3:1, 2.5:1, 2:1, 1.5:1, 1.
  • a 2-80 mM buffer e.g., an acetate buffer or a histamine buffer
  • stabilizers e.g., mannito
  • the pharmaceutical composition comprises an aqueous solution of at least 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.
  • 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., sodium acetate buffer, histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and/or arginine or a pharmaceutically acceptable salt 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 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 6.5, 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.
  • 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
  • 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of anti-PD-1 antibody or its antigen-binding fragment, and 200 mg, 300 mg, or 400 mg, or multiples/fractions of anti-LAG-3 antibody or its antigen-binding fragment.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • 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 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, 1:1-5, 1:1-4.5, or 1:1-5.
  • 5-60 mM buffer e.g., acetate buffer or histidine buffer
  • stabilizers
  • 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 5-60 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) 0.08-1.6 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20);
  • 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:
  • 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., sodium acetate buffer, histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and/or arginine or a pharmaceutically acceptable salt 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 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 6.5, 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.
  • 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
  • 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of anti-PD-1 antibody or its antigen-binding fragment, and 200 mg, 300 mg, or 400 mg, or multiples/fractions of anti-LAG-3 antibody or its antigen-binding fragment.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • 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 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, or 1:1-6.
  • a 10-40 mM buffer e.g., an acetate buffer or
  • 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment 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,
  • 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., sodium acetate buffer, histidine buffer, or 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.
  • 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
  • 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of anti-PD-1 antibody or its antigen-binding fragment, and 200 mg, 300 mg, or 400 mg, or multiples/fractions of anti-LAG-3 antibody or its antigen-binding fragment.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • 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 10-20 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 80 or polysorbate 20); 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.
  • a 10-20 mM buffer e.g., an acetate buffer or a hist
  • 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 10-20 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, 100, 0.1 mg/mL).
  • a 10-20 mM buffer e.g., an acetate buffer or a histidine buffer
  • stabilizers e.g., mannitol, sorbitol, trehalose, sucrose, proline, arginine or a pharmaceutically acceptable salt thereof, and/
  • 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.
  • 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 10-20 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.
  • a 10-20 mM buffer e.g., a sodium acetate buffer, a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., sucrose, proline, and/or arginine or a pharmaceutically acceptable salt thereof
  • 0.2-0.8 mg/mL or 0.4-0 0.2-0.8 mg/mL or 0.4-0.
  • 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 6.5, 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.
  • 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
  • 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 10-2100 mg, 40-1800 mg, 80-1500 mg, 100-1200 mg, 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of anti-PD-1 antibody or its antigen-binding fragment, and 200 mg, 300 mg, or 400 mg, or multiples/fractions of anti-LAG-3 antibody or its antigen-binding fragment.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • 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., 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 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 6.5, 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.
  • 1-100 mM buffer
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or a multiple/fraction thereof, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 160-800 mg, or 300-600 mg, or a multiple/fraction of any value within the range.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or a multiple/fraction thereof
  • the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 160 mg, 200 mg, 300mg, 400mg, 600mg, or 800mg, or multiples/fractions thereof.
  • the pharmaceutical composition comprises 100mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 200mg, 300mg, or 400mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100mg or 200mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300mg or 600mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 600mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300mg.
  • 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., 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 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 6.5, 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.
  • 2-80 mM buffer
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL. 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 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg.
  • 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., 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.
  • 5-60 mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., 20-200 mg/mL sucrose and/or 100-700 mM proline
  • 0.08-1.6 mg/mL surfactant e.g., 20-200 mg/mL sucrose and/or 100-700 mM proline
  • 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 6.5, 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or a multiple/fraction thereof, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 160-800 mg, or 300-600 mg, or a multiple/fraction of any value within the range.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or a multiple/fraction thereof
  • the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 160 mg, 200 mg, 300mg, 400mg, 600mg, or 800mg, or multiples/fractions thereof.
  • the pharmaceutical composition comprises 100mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 200mg, 300mg, or 400mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100mg or 200mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300mg or 600mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 600mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300mg.
  • 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., 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 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 6.5, 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
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL. 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 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg.
  • 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., 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.
  • mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., 40-180 mg/mL sucrose and/or 150-600 mM proline
  • surfactant e.g., 40-180 mg/mL sucrose and/or 150-600 mM proline
  • polysorbate 80 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 6.5, 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or a multiple/fraction thereof, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 160-800 mg, or 300-600 mg, or a multiple/fraction of any value within the range.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or a multiple/fraction thereof
  • the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 160 mg, 200 mg, 300 mg, 400 mg, 600mg, or 800mg, or multiples/fractions thereof.
  • the pharmaceutical composition comprises 100mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 200mg, 300mg, or 400mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100mg or 200mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300mg or 600mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 600mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300mg.
  • 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 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 6.5, 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL. 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 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg.
  • 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) 10-20 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.
  • mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., 60-180 mg/mL or 70-170 mg/mL sucrose and/or 200-500 mM proline
  • L surfactant e.g., polysorbate 80 or polysorbate 20
  • 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 6.5, 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or its multiple/fraction, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 160-800 mg, or 300-600 mg, or any multiple/fraction of a value within the range.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or its multiple/fraction
  • the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 160mg, 200mg, 300mg, 400mg, 600mg, or 800mg, or multiples/fractions thereof.
  • the pharmaceutical composition comprises 100mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 200mg, 300mg, or 400mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100mg or 200mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300mg or 600mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 600mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300mg.
  • 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., 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 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 6.5, 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.
  • mM buffer e.g., sodium acetate buffer,
  • 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., 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 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 6.5, 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.
  • mM buffer e.g., sodium acetate buffer, his
  • 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 10-20 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.
  • a 10-20 mM buffer e.g., a sodium acetate buffer, a histidine buffer, or a histidine-acetate buffer
  • stabilizers e.g., 60-180 mg/mL sucrose
  • 0.2-0.8 mg/mL or 0.4-0.8 mg/mL of sucrose 0.2-0.8 mg/mL or 0.4-0.8 mg/mL of sucrose.
  • m surfactant e.g., polysorbate 80
  • 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 6.5, 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL. 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 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg.
  • 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., 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 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 6.5, 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.
  • mM buffer e.g.
  • 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 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 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 6.5, 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.
  • mM buffer e.g.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL. 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 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range thereof.
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 200 mg, 300 mg, or 400 mg, or multiples/fractions thereof of an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg.
  • 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) 10-20 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 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 6.5, 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.
  • mM buffer e.g.
  • 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) 10-20 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 dapoxetine.
  • mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., 60-180 mg/mL or 70-170 mg/mL sucrose and 200-500 mM proline
  • g/mL surfactant e.g., polysorbate 80
  • 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 6.5, 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.
  • 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) 10-20 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 table 1.
  • mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g. 80-164.3 mg/mL sucrose and 200-300 mM proline
  • Surfactant e.g., polysorbate 80
  • 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 6.5, 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.
  • 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) 10-20 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 ...
  • 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 6.5.
  • 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) 10-20 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, 274 mM, 284 mM, 292 mM, 306 mM, 312 mM, 364 mM, 376 mM, 384 mM, 396 mM, 406 mM, 416 mM, 424 mM
  • 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) 10-20 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).
  • 10-20 mM histidine buffer e.g., 10 mM or 20 mM histidine-acetate buffer
  • 200-500 mM sucrose e.g., 200 mM, 300 mM, 316 mM, 400 mM, or 500
  • 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.
  • 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) 10-20 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, 233mM, 250mM, or 300mM proline), and (d) 0.4-0.8mg/mL polysorbate 80 (e.g., 0.4mg/mL, 0.5mg/mL, 0.6mg/mL or 0.8mg/mL polysorbate 80); wherein the fixed dose ratio of the
  • 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) 10-20 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).
  • 10-20 mM histidine buffer e.g., 10 mM or 20 mM histidine-acetate buffer
  • 230-480 mM sucrose e.g., 200 mM, 300 mM, 316 mM, 400 mM, or 480 mM sucrose
  • 200-300 mM proline
  • 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.
  • 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) 10-20 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).
  • 10-20 mM histidine buffer e.g., 10 mM or 20 mM histidine-acetate buffer
  • 250-350 mM sucrose e.g., 250 mM, 300 mM, 316 mM, or 350 mM sucrose
  • 200-300 mM proline e.g., 200 mM,
  • 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL. 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 160-800 mg, or 300-600 mg, or multiples/fractions of any value within the range.
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of anti-PD-1 antibody or its antigen-binding fragment, and 200 mg, 300 mg, or 400 mg, or multiples thereof. / fraction of anti-LAG-3 antibody or antigen-binding fragment thereof.
  • 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.
  • 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment is 1:3, and the pH of the pharmaceutical composition is 5 to 6.5,
  • 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) 80-160 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment is 1:3, and the pH of the pharmaceutical composition is 5.3 to 5.8 or 5.5 to 5.8.
  • 20 mM histidine buffer e
  • 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) 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment is 1:3, and the pH of the pharmaceutical composition is 5.3 to 5.8 or 5.5 to 5.8.
  • 20 mM histidine buffer e.g., 20
  • 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) 80-160 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • 20 mM histidine buffer e.
  • 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) 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • 20 mM histidine buffer e.g., 20 mM histidine-acetate buffer
  • 310-320 mM sucrose e
  • 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 4-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-30 mg/mL or 5-20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 5-15 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-LAG-3 antibody or its antigen-binding fragment is 15 mg/mL. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or its multiple/fraction, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 160-800 mg, or 300-600 mg, or any multiple/fraction within the range.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or its multiple/fraction
  • 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.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of anti-PD-1 antibody or its antigen-binding fragment, and 200 mg, 300 mg, or 400 mg, or multiples/fractions of anti-LAG-3 antibody or its antigen-binding fragment.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg or 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 600 mg. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-LAG-3 antibody or its antigen-binding fragment is 300 mg.
  • 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.
  • 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.
  • mM buffer e.g., acetate buffer or hist
  • the pharmaceutical composition of the present disclosure comprises: (a) 2-60 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 3-120 mg/mL 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); 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.
  • mM buffer e.g., acetate buffer or histidine buffer
  • stabilizers e.g.,
  • the pharmaceutical composition of the present disclosure comprises: (a) 3-30 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 4-80 mg/mL 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); 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.
  • 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
  • the pharmaceutical composition of the present disclosure comprises: (a) 4-20 mg/mL or 5-20 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 5-50 mg/mL or 5-40 mg/mL 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 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); 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.
  • mM buffer e.g
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-15 mg/mL or 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 5-30 mg/mL or 5-20 mg/mL anti-LAG-3 antibody or an 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 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 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.
  • the pH of the pharmaceutical composition is
  • 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., sodium acetate buffer, histidine buffer or histidine-acetate buffer), (c) one or more stabilizers (e.g., sucrose, proline, and/or arginine or a pharmaceutically acceptable salt 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.
  • mM buffer e.g., sodium acetate buffer, histidine buffer or histidine-acetate buffer
  • stabilizers e.g
  • 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,
  • the pharmaceutical composition comprises: (a) a stabilizer (e.g., sucrose, proline, and/or arginine, or a pharmaceutically acceptable salt thereof), (b) a stabilizer (e.g., sucrose, proline, and/or arginine, or a pharmaceutically acceptable salt thereof), and (c) 0.04-2 mg/mL of a 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.
  • a surfactant e.g., polysorbate 80
  • the pharmaceutical composition of the present disclosure comprises: (a) 3-30 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 4-80 mg/mL anti-LAG-3 antibody or an 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 a pharmaceutically acceptable salt 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.
  • 5-60 mM buffer e.g., sodium acetate buffer, histidine buffer or histidine-acetate buffer
  • stabilizers e.g., sucrose, proline, and/or
  • the pharmaceutical composition of the present disclosure comprises: (a) 4-20 mg/mL or 5-20 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 5-50 mg/mL or 5-40 mg/mL anti-LAG-3 antibody or an 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 a pharmaceutically acceptable salt 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.
  • mM buffer e.g., sodium acetate buffer, histidine buffer or histidine-acetate buffer
  • the pharmaceutical composition of the present disclosure comprises: (a) 1-100 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 1-200 mg/mL 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 (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.
  • mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., 1-400 mg/mL sucrose and/or 10-1000
  • the pharmaceutical composition of the present disclosure comprises: (a) 1-80 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 2-160 mg/mL 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 (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.
  • mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., 1-400 mg/mL sucrose and/or 10-1000
  • the pharmaceutical composition of the present disclosure comprises: (a) 2-60 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 3-120 mg/mL 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 (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.
  • 2-80 mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., 10-300 mg/mL sucrose and/or
  • the pharmaceutical composition of the present disclosure comprises: (a) 3-30 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 4-80 mg/mL 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); 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.
  • 5-60 mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., 20-200 mg/mL sucrose
  • the pharmaceutical composition of the present disclosure comprises: (a) 4-20 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 5-50 mg/mL 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); 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.
  • mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., 40-200 mg/mL sucrose and/
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-20 mg/mL of 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., 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 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.
  • mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., 40-180 mg/mL sucrose and/or 150
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-15 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 5-30 mg/mL 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); 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.
  • mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., 60-180 mg/mL sucrose and/
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 5-20 mg/mL 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 200-500 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.
  • 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
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 5-15 mg/mL 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., 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.
  • mM buffer e.g., a histidine buffer or a histidine-acetate buffer
  • stabilizers e.g., 70-170 mg/mL sucrose and/
  • 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).
  • 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.
  • 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
  • the pharmaceutical composition has a pH of 5 to 6.5, 5 to 6.3, 5.3 to 6.3, 5.3
  • 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).
  • 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.
  • 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),
  • the pharmaceutical composition comprises (a) 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 (b) 0.2-0.8 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.2 mg/mL, 0.4
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 5-20 mg/mL or 5-15 mg/mL anti-LAG-3 antibody or an 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 (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
  • 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 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 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.
  • 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.
  • 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 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
  • the pharmaceutical composition comprises (a) 1-200 mM sodium dextrose (e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM, or 500 mM proline), and (b) 0.1-1 mg/mL polysorbate 80 (e.g.,
  • 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 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 mM sucrose).
  • 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.
  • 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.
  • 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).
  • 10-20 mM histidine buffer or histidine-acetate buffer e.g., 10 mM or 20 mM histidine buffer or histidine-acetate buffer
  • 60-180 mg/mL or 70-170 mg/mL sucrose e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/
  • mM proline e.g., 200 mM, 233 mM, 250 mM, 300 mM, 400 mM, 480 mM or 500 mM proline
  • 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
  • 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.
  • 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 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 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
  • 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 histidine buffer (e.g., 10 mM or 20 mM 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 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
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-15 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 5-30 mg/mL 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,
  • the pharmaceutical composition comprises (a) 0.1-0.2 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) 0.1-0.2 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/
  • the pharmaceutical composition of the present disclosure 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 (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 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
  • the pharmaceutical composition of the present disclosure 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 (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/m
  • the pharmaceutical composition of the present disclosure 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 (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) 0.1-0.5 mg/mL sucrose and (b) 0.2-1.5 mg/mL sucrose and (c) 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 (
  • the pharmaceutical composition of the present disclosure 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 (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).
  • the present invention provides an aqueous solution of at least 200 mM of oligosaccharides and at least 200 mM of oligosaccharides (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.
  • 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.
  • the pharmaceutical composition of the present disclosure 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 (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,
  • 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
  • the pharmaceutical composition comprises (a) 0.5-1.0 mg/mL sucrose and (b) 200-500 mM proline (e.g., 200 mM, 233 mM, 250 mM, or 300 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
  • 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 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); and the pH of the pharmaceutical composition is 5
  • 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) 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,
  • 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) 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).
  • the present invention provides an aqueous solution of at least 200 mM of oligosaccharides and at least 200 mM of oligosaccharides (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.
  • 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.
  • 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
  • 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) 0.5-0.8 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
  • 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 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 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
  • 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 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 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
  • 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).
  • 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.
  • 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
  • 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 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
  • 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).
  • 20 mM histidine buffer e.g., 20 mM histidine-acetate buffer
  • 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.
  • 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,
  • 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).
  • 20 mM histidine buffer e.g., 20 mM histidine-acetate buffer
  • 80-164.3 mg/mL sucrose e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 108.1 mg/mL.
  • the pharmaceutical composition comprises (a) 0.1 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; 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.
  • the pharmaceutical composition of the present disclosure comprises: (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 (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.
  • 20 mM histidine buffer e.g., 20 mM histidine-a
  • the pharmaceutical composition of the present disclosure comprises: (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 (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.
  • 20 mM histidine buffer e.g., 20 mM histidine-acetate buffer
  • 80-160 mg/mL sucrose e.g., 80 mg/mL, 8
  • 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.
  • sucrose e.g. 80 mg/mL, 85.6 mg/
  • 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 acid (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
  • the pharmaceutical composition of the present disclosure comprises: (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 (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.
  • 20 mM histidine buffer e.g., 20 mM histidine-acetate buffer
  • 80 mg/mL sucrose and 200 mM proline 0.8 mg/mL polysorbate 80
  • the pH of the pharmaceutical composition is 5.5 to 5.8.
  • the pharmaceutical composition of the present disclosure comprises: (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 (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.
  • 20 mM histidine buffer e.g., 20 mM histidine-acetate buffer
  • 80 mg/mL sucrose and 300 mM proline 0.8 mg/mL polysorbate 80
  • the pH of the pharmaceutical composition is 5.5 to 5.8.
  • the pharmaceutical composition of the present disclosure comprises: (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 (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.
  • 20 mM histidine buffer e.g., 20 mM histidine-acetate buffer
  • 160 mg/mL or 164.3 mg/mL sucrose and 200 mM proline 0.8 mg/mL polysorbate 80
  • the pH of the pharmaceutical composition is 5.5 to 5.8.
  • the pharmaceutical composition of the present disclosure comprises: (a) 4-6 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 12-18 mg/mL anti-LAG-3 antibody or an 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.
  • mM histidine buffer e.g., 20 mM histidine-acetate buffer
  • 80-120 mg/mL sucrose e.g., 108.1 mg/mL sucrose
  • 180-240 mM proline e.g., 200 mM proline
  • the pharmaceutical composition of the present disclosure comprises: (a) 4-6 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 12-18 mg/mL anti-LAG-3 antibody or an 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.
  • mM histidine buffer e.g. 20 mM histidine-acetate buffer
  • 100-120 mg/mL sucrose e.g., 108.1 mg/mL sucrose
  • 180-240 mM proline e.g., 200 mM proline
  • the pharmaceutical composition of the present disclosure comprises: (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 (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.
  • 20 mM histidine buffer e.g., 20 mM histidine-acetate buffer
  • 108.1 mg/mL sucrose and 200 mM proline 0.8 mg/mL polysorbate 80
  • the pH of the pharmaceutical composition is 5.5 to 5.8.
  • the pharmaceutical composition of the present disclosure comprises: (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 (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.
  • 20 mM histidine buffer e.g., 20 mM histidine-acetate buffer
  • 316 mM sucrose and 200 mM proline e.g., 316 mM sucrose and 200 mM proline
  • 0.8 mg/mL polysorbate 80 e.g., 0.8 mg/mL polysorbate 80
  • the pharmaceutical composition of the present disclosure comprises: (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 (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.
  • 20 mM histidine buffer e.g., 20 mM histidine-acetate buffer
  • 108.1 mg/mL sucrose and 200 mM proline 0.8 mg/mL polysorbate 80
  • the pH of the pharmaceutical composition is 5.8.
  • 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.
  • 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.
  • 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.
  • 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.
  • the second antibody or an antigen-binding fragment thereof is an anti-LAG-3 antibody or an antigen-binding fragment thereof.
  • the present disclosure also provides a method for preparing the lyophilized preparation, which includes the step of freeze-drying the pharmaceutical composition of the present disclosure.
  • 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 is 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 is understood by those skilled in the art that in the pharmaceutical field, lyophilized preparations generally have a residual moisture content of about 0.1 to 5% (w/v) and are present as powders or physically stable cakes.
  • 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.
  • 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, which can form a pharmaceutical composition of the present disclosure after reconstitution.
  • the solution used for reconstitution includes but is not limited to water for injection, sodium chloride injection, Ringer's solution or glucose injection.
  • “reconstitution” and “redissolution” are used interchangeably.
  • the anti-PD-1 antibody or antigen-binding fragment thereof disclosed herein 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 (disclosed in CN106977602A, the entire contents of which are incorporated herein by reference).
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region of the amino acid sequence shown in SEQ ID NO:17, and LCDR1, LCDR2 and LCDR3 in the light chain variable region of the amino acid sequence shown in SEQ ID NO:18.
  • the CDR sequences of the anti-PD-1 antibody or antigen-binding fragment thereof are shown in Table 1.
  • CDR complementarity determining region
  • a given antibody or region thereof e.g., variable region
  • CDR regions have been shown in Table 1, however, 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 definitions of AbM, Kabat, CCG, Chothia, IMGT or Contact, etc., which are well known in the art).
  • 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.
  • 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.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region as shown in SEQ ID NO: 17.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain variable region as shown in SEQ ID NO: 18.
  • the anti-PD-1 antibody or its antigen-binding fragment 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 shown in 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 shown in SEQ ID NO:18.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence as shown in SEQ ID NO: 17, and a light chain variable region having an amino acid sequence as shown in SEQ ID NO: 18.
  • 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.
  • the anti-PD-1 antibody or antigen-binding fragment thereof described in the present disclosure comprises a heavy chain variable region and a light chain variable region.
  • 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 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 S
  • NO:18 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.
  • the anti-PD-1 antibody or its antigen-binding fragment may further comprise a constant region of an immunoglobulin, or a fragment, analog, variant or derivative of the constant region.
  • the constant region comprises a heavy chain constant region and a light chain constant region.
  • the heavy chain constant region is from a human immunoglobulin heavy chain, such as a heavy chain of IgG1, IgG2, IgG3 and IgG4 or other classes of immunoglobulins, preferably a heavy chain of IgG1.
  • the light chain constant region is from a human immunoglobulin light chain, such as a ⁇ light chain or a ⁇ light chain of a human immunoglobulin.
  • the present disclosure provides a method for preparing a pharmaceutical composition of the present disclosure, comprising: contacting an anti-LAG-3 antibody or an antigen-binding fragment thereof with a buffer, a stabilizer and a surfactant, contacting an anti-PD-1 antibody or an antigen-binding fragment thereof with a buffer, a stabilizer and a surfactant, and mixing the two in a desired ratio.
  • the step of contacting the antibody or its antigen-binding fragment with a buffer, a stabilizer and a surfactant comprises replacing the antibody or its antigen-binding fragment into a buffer, and then adding a surfactant and a stabilizer, and the surfactant and the stabilizer are added in no particular order.
  • 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 preparation of the present disclosure.
  • the present disclosure also provides the use of the pharmaceutical composition and lyophilized preparation of the present disclosure in the preparation of a medicament for treating an infectious disease.
  • 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.
  • the pharmaceutical composition or lyophilized preparation of the present disclosure can be administered together with an infectious disease therapeutic agent known in the art, such as a vaccine.
  • the present disclosure also provides a medicine box or vial, which contains the pharmaceutical composition or lyophilized preparation of the present disclosure.
  • the medicine box and vial of the present disclosure may also contain instructions for the pharmaceutical composition or lyophilized preparation of the present disclosure for treating 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).
  • the present disclosure also provides a medical device comprising a pharmaceutical composition or lyophilized preparation of the present disclosure.
  • the medical device of the present disclosure may also include instructions for the pharmaceutical composition or lyophilized preparation of the present disclosure for treating a disease.
  • the medical device includes a syringe and an intravenous bag.
  • the syringe or intravenous bag 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).
  • the disease comprises cancer.
  • the cancer is recurrent, refractory, metastatic and/or advanced cancer.
  • the cancer is a non-solid tumor.
  • the cancer is a solid tumor.
  • 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, 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.
  • the head and neck cancer comprises head and neck squamous cell carcinoma.
  • the esophageal cancer comprises esophageal squamous cell carcinoma.
  • the lung cancer comprises small cell lung cancer and non-small cell lung cancer.
  • the liver cancer comprises hepatocellular carcinoma.
  • the kidney cancer comprises renal cell carcinoma.
  • the bladder cancer comprises urothelial carcinoma.
  • the skin cancer comprises melanoma.
  • the lymphoma includes Hodgkin's lymphoma and non-Hodgkin's lymphoma. In some embodiments, the lymphoma includes T-cell non-Hodgkin's lymphoma or B-cell non-Hodgkin's lymphoma.
  • the non-Hodgkin's lymphoma includes primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, peripheral T-cell lymphoma, mantle cell lymphoma, Burkitt's lymphoma, lymphoblastic lymphoma, cutaneous T-cell lymphoma, cutaneous B-cell lymphoma, marginal zone lymphoma, and/or AIDS-related B-cell lymphoma.
  • the blood stream includes myeloma, leukemia, myelodysplastic syndrome, myelofibrosis, and B-cell malignancies.
  • the leukemia includes acute lymphocytic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and chronic myelomonocytic leukemia.
  • the disease includes an infectious disease.
  • 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.
  • the pharmaceutical composition of the present disclosure can be provided in any desired volume.
  • the pharmaceutical composition of the present disclosure is 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.
  • the pharmaceutical composition of the present disclosure is present in a single cavity of a vial, a syringe, or an intravenous bag with a fill volume of 30 mL or 40 mL.
  • 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.
  • Embodiment 2 The pharmaceutical composition according to embodiment 1, 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, 1:1-4.5, 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.
  • Embodiment 3 The pharmaceutical composition according to embodiment 1 or 2, wherein 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.
  • Embodiment 4 The pharmaceutical composition of any one of Embodiments 1-3, wherein 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.
  • 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.
  • 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.
  • Embodiment 7 The pharmaceutical composition according to Embodiments 1-6, wherein the buffer comprises a histidine buffer, an acetate buffer, a Tris buffer, a phosphate buffer or a citrate buffer.
  • the buffer comprises a histidine buffer, an acetate buffer, a Tris buffer, a phosphate buffer or a citrate buffer.
  • Embodiment 8 The pharmaceutical composition according to 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.
  • Embodiment 9 A 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.
  • Embodiment 10 A 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.
  • Embodiment 11 The pharmaceutical composition according to 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.
  • Embodiment 12 A pharmaceutical composition according to any one of embodiments 1-11, wherein the pharmaceutical composition comprises 10-1000mM, 50-800mM, 100-700mM, 100-600mM, 150-600mM, 200-600mM, 200-500mM or 200-300mM proline.
  • Embodiment 13 A pharmaceutical composition according to 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.
  • Embodiment 14 The pharmaceutical composition according to any one of embodiments 1-13, wherein the surfactant comprises polysorbate 80 or polysorbate 20.
  • Embodiment 15 A pharmaceutical composition according to 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.
  • 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.
  • 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.
  • Embodiment 18 A pharmaceutical composition according to any one of Embodiments 1-17, 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.
  • Embodiment 19 A pharmaceutical composition according to any one of Embodiments 1-18, 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) 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3.
  • Embodiment 20 A pharmaceutical composition according to any one of Embodiments 1-19, 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) 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3.
  • Embodiment 21 A pharmaceutical composition according to any one of Embodiments 1-20, 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) 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3.
  • Embodiment 22 A pharmaceutical composition according to any one of Embodiments 1-21, 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) 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3.
  • Embodiment 23 A pharmaceutical composition according to 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 its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment is 1:3, and the pH of the pharmaceutical composition is 5 to 6.3.
  • Embodiment 24 A pharmaceutical composition according to any one of Embodiments 1-23, wherein the pharmaceutical composition comprises: (a) 1-100 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 1-200 mg/mL 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; and the pH of the pharmaceutical composition is 5 to 6.3.
  • Embodiment 25 The pharmaceutical composition according to any one of Embodiments 1-24, wherein the pharmaceutical composition comprises: (a) 5-10 mg/mL An anti-PD-1 antibody or an antigen-binding fragment thereof and 5-30 mg/mL anti-LAG-3 antibody or an 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.
  • Embodiment 26 A pharmaceutical composition according to any one of Embodiments 1-25, wherein the pharmaceutical composition comprises: (a) 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 5-30 mg/mL 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; and the pH of the pharmaceutical composition is 5 to 6.3.
  • Embodiment 27 A pharmaceutical composition according to 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.
  • Embodiment 28 A pharmaceutical composition according to any one of Embodiments 1-27, wherein the pharmaceutical composition comprises: (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) 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.
  • Embodiment 29 A pharmaceutical composition according to any one of Embodiments 1-28, wherein the pharmaceutical composition comprises: (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.
  • Embodiment 30 A pharmaceutical composition according to any one of Embodiments 1-29, wherein the anti-PD-1 antibody or its antigen-binding fragment 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.
  • Embodiment 31 A pharmaceutical composition according to any one of Embodiments 1-30, wherein the anti-PD-1 antibody or its antigen-binding fragment comprises: a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in 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 shown in SEQ ID NO: 18.
  • Embodiment 32 A pharmaceutical composition according to any one of Embodiments 1-31, wherein the anti-PD-1 antibody or its antigen-binding fragment 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.
  • Embodiment 33 A pharmaceutical composition according to any one of Embodiments 1-32, wherein the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • Embodiment 34 A pharmaceutical composition according to any one of Embodiments 1-33, wherein the anti-LAG-3 antibody or its antigen-binding fragment comprises: a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:7, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:8; or a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:27, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:28.
  • Embodiment 35 A pharmaceutical composition according to any one of Embodiments 1-34, wherein the anti-LAG-3 antibody or its antigen-binding fragment 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.
  • Embodiment 36 A lyophilized preparation, wherein the lyophilized preparation is prepared by lyophilizing the pharmaceutical composition according to any one of Embodiments 1 to 35.
  • the lyophilized preparation can be obtained by freeze-drying; or the lyophilized preparation can be reconstituted to form the pharmaceutical composition according to any one of embodiments 1-35.
  • 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.
  • 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.
  • Embodiment 39 The use according to embodiment 38, wherein the disease comprises cancer and an infectious disease.
  • Embodiment 40 The use according to Embodiment 39, wherein the cancer is recurrent, refractory, metastatic and/or advanced cancer.
  • 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.
  • head and neck cancer nasopharyngeal cancer, oral cancer, esophageal cancer, lung cancer, liver cancer, colon cancer, colorectal cancer, kidney cancer, endometrial cancer, cervical cancer, glioblastom
  • Embodiment 42 The use according to any one of embodiments 38-41, wherein the pharmaceutical composition or lyophilized preparation is suitable for parenteral administration.
  • the heavy chain amino acid sequence of the anti-LAG-3 antibody in the embodiment is shown in SEQ ID NO: 9 of the present disclosure, and the light chain amino acid sequence is shown in SEQ ID NO: 10 of the present disclosure.
  • the heavy chain amino acid sequence of the anti-PD-1 antibody in the embodiment is shown in SEQ ID NO: 19 of the present disclosure, and the light chain amino acid sequence is shown in SEQ ID NO: 20 of the present disclosure.
  • Acetic acid-sodium acetate buffer prepared from acetic acid and sodium acetate trihydrate.
  • 20 mM acetic acid-sodium acetate buffer pH 6.0
  • 20 mM acetic acid-sodium acetate buffer pH 6.0
  • Histidine-HCl buffer prepared with L-histidine and adjusted to the target pH with hydrochloric acid.
  • 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.
  • Histidine-acetate buffer prepared with L-histidine and adjusted to the target pH with acetic acid.
  • 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.
  • Size exclusion chromatography 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-column, 50mmol/L phosphate buffer-200mmol/L sodium chloride solution (pH 7.0) was used as mobile phase for elution, and the detection wavelength was 280nm. The peak area percentages of high molecular impurities and main peaks were calculated by area normalization method.
  • Size exclusion chromatography SEC-HPLC: Thermo high performance liquid chromatograph, TOSOH, TSKgel G3000 SW XL (7.8mm ⁇ 30cm, 5 ⁇ m) chromatographic column, TOSOH, TSKgel G3000 guardcolumn SW XL (6mm ⁇ 4cm, 7 ⁇ m) as pre-column, 50mmol/L phosphate buffer-300mmol/L sodium chloride-200mmol/L arginine hydrochloride (pH7.0) as mobile phase for elution. The components were eluted in descending order of molecular weight and detected at a wavelength of 280nm. The peak area percentage of high molecular impurities and main peak was calculated by area normalization method.
  • Non-reducing sodium dodecyl sulfate capillary electrophoresis (non-reducing CE-SDS): Beckman Coulter Pa 800Plus Biopharmaceutical Analysis System, non-coated fused silica capillary (inner diameter 50 ⁇ m), PDA detector, detection at a detection wavelength of 220nm.
  • the corrected peak area percentages of the main peak and low molecular weight impurities were calculated by area normalization method.
  • Unfolding temperature (Tm) A protein stability analyzer (NanoTemper, Prometheus NT.48) was used to analyze the unfolding temperature (Tm) of the sample. 10 ⁇ L of sample was taken by capillary and placed in the sample chamber. The procedure was as follows: the scanning start temperature was 25°C, the scanning end temperature was 95°C, and the heating rate was 0.3°C/min.
  • the Aggregation temperature (Tagg) of the sample was analyzed using a multi-well plate direct-reading dynamic and static light scattering instrument (Wyatt, Dynaproplate ReaderIII). After the sample was centrifuged, 30 ⁇ L 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 The bubbles were then detected with the following program: temperature program from 25°C to 85°C with a scan time of 5 seconds.
  • Particle size The particle size of the sample was measured using a nanoparticle size analyzer (Malvern, ZEN3600) with the following procedure: temperature 25°C, equilibrium time 120 s.
  • the anti-LAG-3 antibody is replaced into the buffer of Table 3-1, concentrated after the replacement, and then the surfactant and stabilizer are added according to Table 3-1 to obtain the anti-LAG-3 antibody stock solution.
  • the anti-PD-1 antibody stock solution is prepared in the same way.
  • the anti-LAG-3 antibody stock solution and the anti-PD-1 antibody stock solution are mixed evenly in proportion to obtain the pharmaceutical composition Fa1-Fa6, wherein the concentration of the anti-LAG-3 antibody is 4 mg/mL and the concentration of the anti-PD-1 antibody is 12 mg/mL.
  • the pharmaceutical composition is sterilized by filtering through a 0.22 ⁇ m filter membrane, and dispensed into a vial, stoppered and capped.
  • the pharmaceutical composition shown in Table 3-1 was subjected to Tm and Tagg tests, and the test results are shown in Table 3-2. The results show that the conformational stability and colloidal stability of the antibody are good in the pH range of 5.0-7.0.
  • the pharmaceutical composition shown in Table 3-1 was placed at 40°C for 1 week and 2 weeks, and the SEC-UPLC test results are shown in Table 3-3.
  • the anti-LAG-3 antibody is replaced into the buffer of Table 4-1, concentrated after the replacement, and then the surfactant and stabilizer are added according to Table 4-1 to obtain the anti-LAG-3 antibody stock solution.
  • the anti-PD-1 antibody stock solution is prepared in the same way.
  • the anti-LAG-3 antibody stock solution and the anti-PD-1 antibody stock solution are mixed evenly in proportion to obtain the pharmaceutical composition Fb1-Fb6, wherein the concentration of the anti-LAG-3 antibody is 15 mg/mL and the concentration of the anti-PD-1 antibody is 5 mg/mL.
  • the pharmaceutical composition is sterilized by filtering through a 0.22 ⁇ m filter membrane, and dispensed into a vial, stoppered and capped.
  • the pharmaceutical composition shown in Table 4-1 was subjected to Tm and Tagg tests, and the test results are shown in Table 4-2. The results show that the conformational stability and colloidal stability of the antibody are good 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, and the SEC-HPLC and non-reducing CE-SDS test results are shown in Table 4-3. The results show that 80-164.3 mg/mL sucrose has a good effect on maintaining antibody stability.
  • the anti-LAG-3 antibody is replaced into the buffer of Table 5-1, concentrated after the replacement, and then the surfactant and stabilizer are added according to Table 5-1 to obtain the anti-LAG-3 antibody stock solution.
  • the anti-PD-1 antibody stock solution is prepared in the same way.
  • the anti-LAG-3 antibody stock solution and the anti-PD-1 antibody stock solution are mixed evenly in proportion to obtain a pharmaceutical composition Fc1-Fc5, wherein the concentration of the anti-LAG-3 antibody is 15 mg/mL and the concentration of the anti-PD-1 antibody is 5 mg/mL.
  • the pharmaceutical composition is sterilized by filtration through a 0.22 ⁇ m filter membrane, and dispensed into vials, stoppered and capped.
  • 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, and the results show that histidine-acetate buffer is superior to acetate-sodium acetate buffer.
  • the anti-LAG-3 antibody is replaced into the buffer of Table 6-1, concentrated after the replacement, and then the surfactant and stabilizer are added according to Table 6-1 to obtain the anti-LAG-3 antibody stock solution.
  • the anti-PD-1 antibody stock solution is prepared in the same way.
  • the anti-LAG-3 antibody stock solution and the anti-PD-1 antibody stock solution are mixed evenly in proportion to obtain pharmaceutical compositions Fd1 and Fd2, wherein the concentration of the anti-LAG-3 antibody is 15 mg/mL and the concentration of the anti-PD-1 antibody is 5 mg/mL.
  • the pharmaceutical composition is sterilized by filtration through a 0.22 ⁇ m filter membrane, and dispensed into vials, stoppered and capped.
  • 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.
  • 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.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Oncology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne une composition pharmaceutique comprenant un anticorps anti-PD-1 et un second anticorps. Le second anticorps est un anticorps anti-LAG-3. L'invention concerne en outre un procédé de préparation de la composition pharmaceutique et une utilisation de la composition pharmaceutique dans la préparation d'un médicament pour le traitement de maladies d'un sujet.
PCT/CN2024/118665 2023-09-13 2024-09-13 Composition pharmaceutique comprenant un anticorps anti-pd-1 et un second anticorps Pending WO2025056011A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN202311181084.9 2023-09-13
CN202311181084 2023-09-13
CN202410962244 2024-07-17
CN202410962244.1 2024-07-17

Publications (1)

Publication Number Publication Date
WO2025056011A1 true WO2025056011A1 (fr) 2025-03-20

Family

ID=95020946

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2024/118665 Pending WO2025056011A1 (fr) 2023-09-13 2024-09-13 Composition pharmaceutique comprenant un anticorps anti-pd-1 et un second anticorps

Country Status (1)

Country Link
WO (1) WO2025056011A1 (fr)

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106977602A (zh) * 2016-08-23 2017-07-25 中山康方生物医药有限公司 一种抗 pd1 单克隆抗体、其药物组合物及其用途
CN109069643A (zh) * 2016-05-12 2018-12-21 Ucb生物制药私人有限公司 药物组合物
WO2019120269A1 (fr) * 2017-12-22 2019-06-27 江苏恒瑞医药股份有限公司 Composition pharmaceutique à anticorps anti-lag-3 et son utilisation
CN110062766A (zh) * 2016-10-13 2019-07-26 西福根有限公司 抗lag-3抗体及组合物
CN110404066A (zh) * 2018-04-28 2019-11-05 齐鲁制药有限公司 一种抗人pd-1的单克隆抗体制剂、联合用药物及其用途
CN110678200A (zh) * 2017-05-30 2020-01-10 百时美施贵宝公司 包含抗lag-3抗体或抗lag-3抗体和抗pd-1或抗pd-l1抗体的组合物
CN112300280A (zh) * 2019-08-02 2021-02-02 正大天晴康方(上海)生物医药科技有限公司 一种抗pd-1抗体及其医药用途
WO2022184074A1 (fr) * 2021-03-03 2022-09-09 正大天晴药业集团股份有限公司 Composition pharmaceutique contenant un anticorps anti-tslp
CN111094339B (zh) * 2017-10-17 2023-01-24 江苏恒瑞医药股份有限公司 抗pd-1抗体和抗lag-3抗体联合在制备治疗肿瘤的药物中的用途
WO2023025217A1 (fr) * 2021-08-26 2023-03-02 正大天晴药业集团股份有限公司 Composition pharmaceutique d'anticorps anti-il4r et utilisation associée

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109069643A (zh) * 2016-05-12 2018-12-21 Ucb生物制药私人有限公司 药物组合物
CN106977602A (zh) * 2016-08-23 2017-07-25 中山康方生物医药有限公司 一种抗 pd1 单克隆抗体、其药物组合物及其用途
CN110062766A (zh) * 2016-10-13 2019-07-26 西福根有限公司 抗lag-3抗体及组合物
CN110678200A (zh) * 2017-05-30 2020-01-10 百时美施贵宝公司 包含抗lag-3抗体或抗lag-3抗体和抗pd-1或抗pd-l1抗体的组合物
CN111094339B (zh) * 2017-10-17 2023-01-24 江苏恒瑞医药股份有限公司 抗pd-1抗体和抗lag-3抗体联合在制备治疗肿瘤的药物中的用途
WO2019120269A1 (fr) * 2017-12-22 2019-06-27 江苏恒瑞医药股份有限公司 Composition pharmaceutique à anticorps anti-lag-3 et son utilisation
CN110404066A (zh) * 2018-04-28 2019-11-05 齐鲁制药有限公司 一种抗人pd-1的单克隆抗体制剂、联合用药物及其用途
CN112300280A (zh) * 2019-08-02 2021-02-02 正大天晴康方(上海)生物医药科技有限公司 一种抗pd-1抗体及其医药用途
WO2022184074A1 (fr) * 2021-03-03 2022-09-09 正大天晴药业集团股份有限公司 Composition pharmaceutique contenant un anticorps anti-tslp
WO2023025217A1 (fr) * 2021-08-26 2023-03-02 正大天晴药业集团股份有限公司 Composition pharmaceutique d'anticorps anti-il4r et utilisation associée

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MARKUS ZETTL: "Combination of two novel blocking antibodies, anti-PD-1 antibody ezabenlimab (BI 754091) and anti-LAG-3 antibody BI 754111, leads to increased immune cell responses", ONCOIMMUNOLGY, LANDES BIOSCIENCE, US, vol. 11, no. 1, 31 December 2022 (2022-12-31), US , XP093159105, ISSN: 2162-4011, DOI: 10.1080/2162402X.2022.2080328 *
TAWBI, H. A. ET AL.: "Relatlimab and Nivolumab Versus Nivolumab in Untreated Advanced Melanoma", THE NEW ENGLAND JOURNAL OF MEDICINE, 6 January 2022 (2022-01-06), pages 24 - 34, XP009532953, DOI: 10.1056/NEJMoa2109970 *

Similar Documents

Publication Publication Date Title
US20250074985A1 (en) Stable formulations of anti-ctla4 antibodies alone and in combination with programmed death receptor 1 (pd-1) antibodies and methods of use thereof
US20240182573A1 (en) Stable formulations of anti-tigit antibodies alone and in combination with programmed death receptor 1 (pd-1) antibodies and methods of use thereof
CN107743401B (zh) 包含抗pd-1抗体和另外的抗体的组合的组合物
CN110869002A (zh) 程序性死亡受体1(pd-1)抗体的稳定制剂及其使用方法
CN118356488A (zh) 包含抗lag-3抗体或抗lag-3抗体和抗pd-1或抗pd-l1抗体的组合物
CN113797333A (zh) 一种新型冠状病毒抗体的药物组合物及其用途
JP2024528724A (ja) 抗ｐｄ－１抗体医薬組成物及びその使用
CN119173272A (zh) 含有pd-1抗体的稳定高浓度精氨酸配制品及其使用方法
AU2021207586A1 (en) Method of treating a tumor with a combination of IL-7 protein and a bispecific antibody
WO2025056011A1 (fr) Composition pharmaceutique comprenant un anticorps anti-pd-1 et un second anticorps
TW202330027A (zh) 抗ｃｄ－４７抗體製劑
WO2025056014A1 (fr) Composition pharmaceutique comprenant un anticorps anti-pd-1 et un second anticorps
KR20220129548A (ko) 생물제약 조성물 및 관련 방법
WO2020156500A1 (fr) Utilisation d'un anticorps anti-pd-l1 dans le traitement du cancer de la tête et du cou
WO2025056005A1 (fr) Composition pharmaceutique d'anticorps anti-tim-3 et son utilisation
WO2024129555A1 (fr) Lyosphères contenant des anticorps de récepteur de mort programmée 1 (pd-1) et procédés d'utilisation associés
CN119585434A (zh) 抗pd-l1/抗-4-1bb双特异性抗体制剂
CN118526572A (zh) c-Met激酶抑制剂和抗PD-1抗体-TGFβRII融合蛋白的药物组合
BR122024020499A2 (pt) Formulação de anticorpos terapêuticos e uso da mesma

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24864725

Country of ref document: EP

Kind code of ref document: A1