WO2025232811A1 - Anticorps ciblant le récepteur 2iib du facteur de croissance des fibroblastes et son utilisation - Google Patents

Anticorps ciblant le récepteur 2iib du facteur de croissance des fibroblastes et son utilisation

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Publication number
WO2025232811A1
WO2025232811A1 PCT/CN2025/093309 CN2025093309W WO2025232811A1 WO 2025232811 A1 WO2025232811 A1 WO 2025232811A1 CN 2025093309 W CN2025093309 W CN 2025093309W WO 2025232811 A1 WO2025232811 A1 WO 2025232811A1
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Prior art keywords
seq
amino acid
acid sequence
sequence shown
variable region
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PCT/CN2025/093309
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English (en)
Chinese (zh)
Inventor
甄子朋
黄梁敏
马元婧
吕彩云
王亮亮
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Chia Tai Tianqing Pharmaceutical Group Co Ltd
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Chia Tai Tianqing Pharmaceutical Group Co Ltd
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Publication of WO2025232811A1 publication Critical patent/WO2025232811A1/fr
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    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Definitions

  • This disclosure belongs to the field of biomedical technology, specifically relating to antibodies or antigen-binding fragments thereof targeting FGFR2IIIb, and also to the application of said antibodies or antigen-binding fragments thereof.
  • FGFR fibroblast growth factor receptor
  • RTK receptor tyrosine kinase
  • FGFRs bind to their natural ligand, fibroblast growth factor (FGF), undergoing dimerization and autophosphorylation, thereby activating downstream signal transduction pathways.
  • FGF fibroblast growth factor
  • FGFRs consist of three parts: an extracellular region containing the ligand binding site, a single-transmembrane hydrophobic ⁇ -helix region, and an intracellular region containing kinase domains. The extracellular region contains three immunoglobulin-like domains, D1, D2, and D3.
  • FGFR2IIIb is a high-affinity receptor for FGF1 and members of the keratinocyte growth factor (KGF) family (including FGF7, FGF10, and FGF22).
  • KGF keratinocyte growth factor
  • FGFR2IIIb has been found to be aberrantly expressed, such as overexpressed or amplified, in various tumors.
  • FGF7 and FGFR2IIIb are overexpressed in many pancreatic cancers, and their co-expression is associated with poor prognosis (Cho et al., Am.J. Pathol. 170:1964, 2007).
  • Amplification and overexpression of FGFR2 are associated with undifferentiated diffuse gastric cancer, which has a particularly poor prognosis.
  • somatic mutations of the FGFR2 gene, specifically S252W substitution have been found in 12% of endometrial cancers.
  • Several antibodies targeting FGFR2IIIb have been developed as potential therapeutic targets, but the pool remains limited, and more options are needed.
  • This disclosure provides an anti-FGFR2IIIb antibody and its antigen-binding fragment, as well as related nucleic acids, vectors, cells, pharmaceutical compositions, preparation methods, and uses encoding the provided antibody and its antigen-binding fragment.
  • this disclosure provides an anti-FGFR2IIIb antibody or its antigen-binding fragment, comprising:
  • HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6;
  • HCDR1 containing the amino acid sequence shown in SEQ ID NO:33 HCDR2 containing the amino acid sequence shown in SEQ ID NO:34
  • HCDR3 containing the amino acid sequence shown in SEQ ID NO:35 LCDR1 containing the amino acid sequence shown in SEQ ID NO:36
  • LCDR2 containing the amino acid sequence shown in SEQ ID NO:37 HCDR3 containing the amino acid sequence shown in SEQ ID NO:38.
  • this disclosure provides an anti-FGFR2IIIb antibody or its antigen-binding fragment, comprising:
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:7, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:8;
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:39, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:40;
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:61, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:64;
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:62, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:64;
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:63, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:64;
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:66, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:68;
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:67, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:69;
  • HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:96, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO:97; or
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:98, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:99.
  • this disclosure provides isolated nucleic acids containing nucleotide sequences encoding the anti-FGFR2IIIb antibody or its antigen-binding fragment as described in this disclosure.
  • this disclosure provides a carrier containing the nucleic acid described herein.
  • this disclosure provides a host cell containing the nucleic acid or the vector described in this disclosure.
  • this disclosure provides a fusion protein comprising the anti-FGFR2IIIb antibody of this disclosure or an antigen-binding fragment thereof.
  • this disclosure provides antibody-drug conjugates comprising the anti-FGFR2IIIb antibody of this disclosure or an antigen-binding fragment thereof.
  • this disclosure provides an anti-FGFR2IIIb chimeric antigen receptor comprising the anti-FGFR2IIIb antibody of this disclosure or its antigen-binding fragment.
  • this disclosure provides engineered immune effector cells that contain the chimeric antigen receptor of this disclosure.
  • this disclosure provides a method for preparing the anti-FGFR2IIIb antibody or its antigen-binding fragment as described herein, comprising culturing the host cells to express the anti-FGFR2IIIb antibody or its antigen-binding fragment, and isolating and purifying the anti-FGFR2IIIb antibody or its antigen-binding fragment in the system.
  • compositions comprising the anti-FGFR2IIIb antibody or its antigen-binding fragment, the fusion protein, the antibody-drug conjugate or the engineered immune effector cells, and pharmaceutically acceptable excipients.
  • this disclosure provides the use of the anti-FGFR2IIIb antibody or its antigen-binding fragment, the fusion protein, the antibody-drug conjugate, the engineered immune effector cells, or the pharmaceutical composition in the preparation of a medicament for treating diseases expressing FGFR2IIIb.
  • this disclosure provides a method for treating diseases expressing FGFR2IIIb, comprising administering to a subject the anti-FGFR2IIIb antibody or an antigen-binding fragment thereof, the fusion protein, the antibody-drug conjugate, the engineered immune effector cells, or the pharmaceutical composition.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment disclosed herein exhibits good anti-tumor efficacy and/or safety.
  • Figure 1 shows the binding curves of anti-FGFR2IIIb chimeric antibody and human FGFR2IIIb-His protein detected by ELISA
  • Figures 2A-2H show the binding curves of anti-FGFR2IIIb antibody and FGFR2IIIb-expressing cells as detected by FACS.
  • Figures 2A-2D show the binding curves of chimeric antibody ch-Ab13 and its humanized antibody with KATOIII cells, SNU-16 cells, HEK293T-hFGFR2IIIb cells, or HEK293T-hFGFR2IIIb (S252W) cells, respectively.
  • Figures 2E-2H show the binding curves of chimeric antibody ch-Ab41 and its humanized antibody with KATOIII cells, SNU-16 cells, HEK293T-hFGFR2IIIb cells, or HEK293T-hFGFR2IIIb (S252W) cells, respectively.
  • Figures 3A-3C show the binding curves of chimeric antibody ch-Ab13 and its humanized antibody with FGFR1IIIb-His protein, FGFR3IIIb-His protein, or FGFR4-His protein detected by ELISA.
  • Figures 3D-3F show the binding curves of chimeric antibody ch-Ab41 and its humanized antibody with FGFR1IIIb-His protein, FGFR3IIIb-His protein, or FGFR4-His protein detected by ELISA.
  • Figure 4A shows the binding curves of chimeric antibody ch-Ab13 and its humanized antibody with HEK293T-hFGFR2IIIc cells detected by FACS
  • Figure 4B shows the binding curves of chimeric antibody ch-Ab41 and its humanized antibody with HEK293T-hFGFR2IIIc cells detected by FACS.
  • Figures 5A-5C show the ELISA detection of the chimeric antibody ch-Ab13 and its humanized antibody inhibiting FGF1, FGF7 or FGF10-mediated FGFR2IIIb phosphorylation
  • Figures 5D-5F show the ELISA detection of the chimeric antibody ch-Ab41 and its humanized antibody inhibiting FGF1, FGF7 or FGF10-mediated FGFR2IIIb phosphorylation.
  • Figures 6A and 6B show the ADCC effects of hzAb13-2.1 on KATOIII or SNU-16 cells, respectively.
  • antibody is used in the broadest sense to encompass natural and artificial antibodies of various structures, including but not limited to monoclonal antibodies, polyclonal antibodies, monospecific antibodies and multispecific antibodies (e.g., bispecific antibodies, trispecific antibodies), and various antibody structures of single-chain antibodies, as long as they exhibit the desired antigen-binding activity.
  • antigen-binding fragment refers to one or more fragments of an antibody that retain the function of specifically binding to an antigen.
  • examples covered by the term “antigen-binding fragment” include: (i) Fab fragments: monovalent fragments consisting of VL , VH , CL, and CH1 domains; (ii) F(ab') 2 fragments, bivalent fragments containing two Fab fragments connected by disulfide bridges in the hinge region; (iii) Fd fragments consisting of VH and CH1 domains; (iv) Fv fragments consisting of VL and VH domains of an antibody single arm; (v) dAb fragments consisting of VH domains (see Ward et al., Nature. 341:544-546 (1989)); (vi) separated complementarity-determining regions (CDRs); (vii) nanobodies; and single-chain Fv (scFv).
  • variable domain refers to a domain of an antibody involved in the binding of the antibody to an antigen.
  • natural four-chain antibodies e.g., derived from humans, mice, etc.
  • VH, or VH domain heavy chain variable domain
  • VL, or VL domain light chain variable domain
  • each variable domain of a natural antibody essentially consists of four "frame regions (FRs)” and three “complementarity-determining regions (CDRs).”
  • the four frame regions are referred to as frame region 1 (or FR1), frame region 2 (or FR2), frame region 3 (or FR3), and frame region 4 (or FR4); these frame regions are separated by three complementarity-determining regions, referred to in the art and hereinafter as complementarity-determining regions 1 (or CDR1), 2 (or CDR2), and 3 (or CDR3), respectively. Therefore, the general structure of a variable domain can be represented as: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. Variable domains endow antibodies with antigen specificity because they have antigen-binding sites.
  • CDR complementarity-determining region
  • HVR hypervariant region
  • Natural four-chain antibodies typically contain six CDRs: three in the heavy chain variable region, namely heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3); and three in the light chain variable region, namely light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and light chain CDR3 (LCDR3).
  • CDRs The "contact" definition of CDRs is based on the analysis of available complex crystal structures. In addition, there are definitions such as IMGT and CCG. However, it should be noted that the boundaries of the CDRs (Continuous Derivatives) of the same antibody variable region obtained based on different methods may differ; that is, the CDR sequences of the same antibody variable region defined by different methods may vary. Therefore, when referring to antibodies defined by a specific CDR sequence, the scope of the antibody also includes antibodies defined by CDR sequences of other arbitrary definitions (e.g., one or more combinations of definitions such as Kabat, IMGT, Chothia, Contact, AbM, CCG, etc.).
  • treatment means administering the compounds (e.g., antibodies) or pharmaceutical compositions described in this disclosure to prevent, improve, or eliminate a disease or one or more symptoms associated with said disease, including but not limited to: (i) preventing the occurrence of a disease or disease state in mammals, particularly when such mammals are susceptible to the disease state but have not yet been diagnosed with it; (ii) suppressing a disease or disease state, i.e., halting its development; (iii) alleviating a disease or disease state, even if the disease or disease state subsides; and (iv) reducing any direct or indirect pathological consequences of the disease or disease state.
  • therapeutic effective amount means the amount of the disclosed compound used to treat or prevent a particular disease, condition, or disorder; (ii) to reduce, improve, or eliminate one or more symptoms of a particular disease, condition, or disorder; or (iii) to prevent or delay the onset of one or more symptoms of a particular disease, condition, or disorder described herein.
  • the amount of the disclosed anti-FGFR2IIIb antibody or its antigen-binding fragment, antibody-drug conjugate, engineered immune effector cells, fusion protein, or pharmaceutical composition constituting a “therapeutic effective amount” may vary depending on factors such as the compound or pharmaceutical composition and its ability to elicit a desired response in an individual, the disease state and its severity, the route of administration, and the age, sex, and weight of the mammal to be treated.
  • pharmaceutical acceptable refers to compounds, materials, compositions, and/or dosage forms that, within the bounds of reliable medical judgment, are suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, in proportion to a reasonable benefit/risk ratio.
  • excipient refers to any component other than the active ingredient (e.g., the antibody of this disclosure).
  • the selection of excipients will depend to a great extent on factors such as the specific method of administration, the efficacy of the excipient in terms of solubility and stability, and the nature of the dosage form.
  • isolated refers to a target compound that has been isolated from its natural environment, such as an antibody or its antigen-binding fragment or nucleic acid.
  • Xn and “Xaa” are equivalent and refer to unspecified amino acids, the scope of which is specified by subsequent definitions in the relevant description.
  • EC 50 refers to the antibody concentration at which the induced response is 50% of the maximum response, i.e., half the distance between the maximum response and baseline.
  • EC 50 can be measured by ELISA or FACS analysis or any other method known in the art.
  • K ⁇ sub> D ⁇ /sub> refers to the equilibrium dissociation constant, which is derived from the ratio of the dissociation rate constant (k ⁇ sub> d ⁇ /sub> ) to the binding rate constant ( ka ) (i.e., k ⁇ sub>d ⁇ /sub> / ka ) and is expressed as a molar concentration (M).
  • the K ⁇ sub> D ⁇ /sub> value of an antibody can be determined using methods well established in the art.
  • a preferred method for determining the K ⁇ sub> D ⁇ /sub> of an antibody is by using surface plasmon resonance (SPR) technology, preferably using a biosensor system such as the Biacore surface plasmon resonance system.
  • SPR surface plasmon resonance
  • identity also known as consistency, refers to the percentage of amino acid residues in the sequence to be aligned that are identical to those in the specific amino acid sequence shown herein, after aligning the sequence to be aligned with it and, if necessary, introducing vacancies to achieve the maximum percentage of sequence identity, and without considering any conserved substitutions as part of sequence identity.
  • Amino acid sequence alignment for identity can be performed using various methods within the art, such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Those skilled in the art can determine the appropriate parameters for the aligned sequences, including any algorithm required to achieve maximum alignment across the full length of the compared sequences.
  • subject includes any human or non-human animal.
  • non-human animal includes all vertebrates, such as mammals and non-mammals, including non-human primates, sheep, goats, dogs, cats, horses, cattle, chickens, amphibians, reptiles, etc.
  • the subject according to this disclosure is a human.
  • the terms “patient” or “subject” may be used interchangeably.
  • “about” means within the acceptable range of error 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, in accordance with art practice, mean within one or more standard deviations. Alternatively, “about” may mean a range of up to ⁇ 5%, such as fluctuations within ⁇ 2%, ⁇ 1%, or ⁇ 0.5% of a given specific numerical range. When a particular value is given in the scope of this disclosure, unless otherwise stated, “about” shall be understood to mean within the acceptable range of error for that particular value. In this document, unless otherwise stated, the values of step parameters or conditions are implicitly modified by “about”.
  • an anti-FGFR2IIIb antibody or its antigen-binding fragment comprising: HCDR1 containing the amino acid sequence shown in SEQ ID NO: 1, 9, 17, 25 or 33; HCDR2 containing the amino acid sequence shown in SEQ ID NO: 2, 10, 18, 26 or 34; HCDR3 containing the amino acid sequence shown in SEQ ID NO: 3, 11, 19, 27 or 35; LCDR1 containing the amino acid sequence shown in SEQ ID NO: 4, 12, 20, 28 or 36; LCDR2 containing the amino acid sequence shown in SEQ ID NO: 5, 13, 21, 29 or 37; and LCDR3 containing the amino acid sequence shown in SEQ ID NO: 6, 14, 22, 30 or 38.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:9, HCDR2 containing the amino acid sequence shown in SEQ ID NO:10, HCDR3 containing the amino acid sequence shown in SEQ ID NO:11, LCDR1 containing the amino acid sequence shown in SEQ ID NO:12, LCDR2 containing the amino acid sequence shown in SEQ ID NO:13, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:14.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:17, HCDR2 containing the amino acid sequence shown in SEQ ID NO:18, HCDR3 containing the amino acid sequence shown in SEQ ID NO:19, LCDR1 containing the amino acid sequence shown in SEQ ID NO:20, LCDR2 containing the amino acid sequence shown in SEQ ID NO:21, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:22.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:25, HCDR2 containing the amino acid sequence shown in SEQ ID NO:26, HCDR3 containing the amino acid sequence shown in SEQ ID NO:27, LCDR1 containing the amino acid sequence shown in SEQ ID NO:28, LCDR2 containing the amino acid sequence shown in SEQ ID NO:29, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:30.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:33, HCDR2 containing the amino acid sequence shown in SEQ ID NO:34, HCDR3 containing the amino acid sequence shown in SEQ ID NO:35, LCDR1 containing the amino acid sequence shown in SEQ ID NO:36, LCDR2 containing the amino acid sequence shown in SEQ ID NO:37, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:38.
  • This disclosure also provides an anti-FGFR2IIIb antibody or its antigen-binding fragment comprising: HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 7, 15, 23, 31, 39, 61, 62, 63, 66, 67, 96, or 98, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 8, 16, 24, 32, 40, 64, 65, 68, 69, 97, or 99, wherein the CDRs are defined according to Kabat, IMGT, Chothia, Contact, AbM, and/or CCG.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:7, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:8.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:15, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:16.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:23, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:24.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:31, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:32.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:39, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:40.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:61, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO:64.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:62, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:64.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:63, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:64.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:61, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:65.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:62, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO:65.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:63, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:65.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:66, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:68.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:67, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:68.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:66, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:69.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:67, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:69.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:96, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:97.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:98, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:99.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 7, 15, 23, 31, 39, 61, 62, 63, 66, 67, 96, or 98.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 8, 16, 24, 32, 40, 64, 65, 68, 69, 97, or 99.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% of the amino acid sequence shown in SEQ ID NO: 7, 15, 23, 31, 39, 61, 62, 63, 66, 67, 96, or 98.
  • the heavy chain variable region is 99% or 100% identical to the amino acid sequence shown in SEQ ID NO: 8, 16, 24, 32, 40, 64, 65, 68, 69, 97 or 99, and the light chain variable region is at least 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: 8, 16, 24, 32, 40, 64, 65, 68, 69, 97 or 99.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO:7.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO:8.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:7, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:8.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 15.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 16.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:15, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:16.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:9, HCDR2 containing the amino acid sequence shown in SEQ ID NO:10, HCDR3 containing the amino acid sequence shown in SEQ ID NO:11, LCDR1 containing the amino acid sequence shown in SEQ ID NO:12, LCDR2 containing the amino acid sequence shown in SEQ ID NO:13, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:14.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:23.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:24.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:23, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:24.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:17, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:18, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:19, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:20, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:21, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:22.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 32.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 32.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:32, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:32.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:25, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:26, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:27, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:28, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:29, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:30.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 39.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 40.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 39, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 40.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:33, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:34, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:35, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:36, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:37, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:38.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 61.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 64.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 64, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 64.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence that is at least 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:62.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 62, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 64.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence that is at least 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:63.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 63, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 64.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence that is at least 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:65.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 65, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 65.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 62, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 65.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 63, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 65.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 66.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 68.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 66, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 68.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:9, HCDR2 containing the amino acid sequence shown in SEQ ID NO:10, HCDR3 containing the amino acid sequence shown in SEQ ID NO:11, LCDR1 containing the amino acid sequence shown in SEQ ID NO:12, LCDR2 containing the amino acid sequence shown in SEQ ID NO:13, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:14.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence that is at least 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:67.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 67, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 68.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:9, HCDR2 containing the amino acid sequence shown in SEQ ID NO:10, HCDR3 containing the amino acid sequence shown in SEQ ID NO:11, LCDR1 containing the amino acid sequence shown in SEQ ID NO:12, LCDR2 containing the amino acid sequence shown in SEQ ID NO:13, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:14.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence that is at least 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:69.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 66, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 69.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:9, HCDR2 containing the amino acid sequence shown in SEQ ID NO:10, HCDR3 containing the amino acid sequence shown in SEQ ID NO:11, LCDR1 containing the amino acid sequence shown in SEQ ID NO:12, LCDR2 containing the amino acid sequence shown in SEQ ID NO:13, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:14.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 67, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 69.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:9, HCDR2 containing the amino acid sequence shown in SEQ ID NO:10, HCDR3 containing the amino acid sequence shown in SEQ ID NO:11, LCDR1 containing the amino acid sequence shown in SEQ ID NO:12, LCDR2 containing the amino acid sequence shown in SEQ ID NO:13, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:14.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 96.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 97.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 96, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 97.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 98.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 99.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 98, and a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 99.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment further comprises: HCDR1 containing the amino acid sequence shown in SEQ ID NO:9, HCDR2 containing the amino acid sequence shown in SEQ ID NO:10, HCDR3 containing the amino acid sequence shown in SEQ ID NO:11, LCDR1 containing the amino acid sequence shown in SEQ ID NO:12, LCDR2 containing the amino acid sequence shown in SEQ ID NO:13, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:14.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:7, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:8.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:15, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:16.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:23, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:24.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:31, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:32.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:39, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:40.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:64.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:62, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:64.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:63, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:64.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:65.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:62, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:65.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:63, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:65.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:66, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:68.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:67, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:68.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:66, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:69.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:67, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:69.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:96, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:97.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:98, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:99.
  • the antigen-binding fragment is a Fab fragment, an F(ab') 2 fragment, an Fd fragment, an Fv fragment, a separated CDR region, or a scFv.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment is murine, chimeric, or humanized. Humanization can reduce immunogenicity. Therefore, in some embodiments, the anti-FGFR2IIIb antibody or its antigen-binding fragment is humanized.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment of the present disclosure may further comprise a constant region of an immunoglobulin, or a fragment, analog, variant, or derivative of said constant region.
  • the constant region comprises a heavy chain constant region and a light chain constant region.
  • the heavy chain constant region is derived from the heavy chain of human immunoglobulins, such as IgG1, IgG2, IgG3, IgG4, or other classes of immunoglobulins.
  • the light chain constant region is derived from the light chain of human immunoglobulins, such as the ⁇ or ⁇ light chain of human immunoglobulins.
  • the anti-FGFR2IIIb antibody is an IgG1, IgG2, IgG3, or IgG4 isotype.
  • the constant region may comprise any modification of the present disclosure or known in the art, such as the insertion, deletion, substitution, or chemical modification of amino acids.
  • the C-terminal lysine of the heavy chain constant region may be present or absent.
  • the constant region comprises a mutation that alters effector function.
  • any amino acid residue of the constant region may be substituted with any allotype amino acid residue.
  • the constant region does not contain fucose.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 41, 45, 49, 53, 57, 70, 72, 74, 80, or 82.
  • the anti-FGFR2IIIb antibody comprises a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 43, 47, 51, 55, 59, 76, 78%, 99%, or 100%.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 41, 45, 49, 53, 57, 70, 72, 74, 80, or 82, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 43, 47, 51, 55, 59, 76, 78, 84, or 86.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:41.
  • the anti-FGFR2IIIb antibody comprises a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:43.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:41, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:43.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:2, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:3, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:4, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:5, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:45.
  • the anti-FGFR2IIIb antibody comprises a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:47.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:45, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:47.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:9, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:10, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:11, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:12, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:13, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:14.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:49.
  • the anti-FGFR2IIIb antibody comprises a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:51.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:49, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:51.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:17, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:18, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:19, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:20, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:21, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:22.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 53.
  • the anti-FGFR2IIIb antibody comprises a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 55.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:53, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:55.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:25, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:26, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:27, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:28, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:29, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:30.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 57.
  • the anti-FGFR2IIIb antibody comprises a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 59.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:57, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:59.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:33, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:34, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:35, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:36, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:37, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:38.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 70.
  • the anti-FGFR2IIIb antibody comprises a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 76.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:70, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:76.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:2, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:3, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:4, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:5, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence that is at least 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:72.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:72, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:76.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:2, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:3, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:4, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:5, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence that is at least 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:74.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:74, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:76.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:2, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:3, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:4, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:5, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody comprises a light chain having an amino acid sequence that is at least 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:78.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:70, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:78.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:2, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:3, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:4, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:5, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:72, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:78.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:2, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:3, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:4, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:5, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:74, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:78.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:2, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:3, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:4, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:5, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:6.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 80.
  • the anti-FGFR2IIIb antibody comprises a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 84.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:80, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:84.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:9, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:10, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:11, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:12, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:13, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:14.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence that is at least 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:82.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:82, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:84.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:9, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:10, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:11, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:12, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:13, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:14.
  • the anti-FGFR2IIIb antibody comprises a light chain having an amino acid sequence that is at least 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:86.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:80, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:86.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:9, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:10, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:11, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:12, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:13, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:14.
  • the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:82, and a light chain having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:86.
  • the anti-FGFR2IIIb antibody further comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:9, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:10, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:11, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:12, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:13, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:14.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain containing the amino acid sequence shown in SEQ ID NO:41, and a light chain containing the amino acid sequence shown in SEQ ID NO:43.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:45, and a light chain comprising the amino acid sequence shown in SEQ ID NO:47.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:49, and a light chain comprising the amino acid sequence shown in SEQ ID NO:51.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain containing the amino acid sequence shown in SEQ ID NO:53, and a light chain containing the amino acid sequence shown in SEQ ID NO:55.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain containing the amino acid sequence shown in SEQ ID NO:57, and a light chain containing the amino acid sequence shown in SEQ ID NO:59.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:70, and a light chain comprising the amino acid sequence shown in SEQ ID NO:76.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain containing the amino acid sequence shown in SEQ ID NO:72, and a light chain containing the amino acid sequence shown in SEQ ID NO:76.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:74, and a light chain comprising the amino acid sequence shown in SEQ ID NO:76.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain containing the amino acid sequence shown in SEQ ID NO:70, and a light chain containing the amino acid sequence shown in SEQ ID NO:78.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain containing the amino acid sequence shown in SEQ ID NO:72, and a light chain containing the amino acid sequence shown in SEQ ID NO:78.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:74, and a light chain comprising the amino acid sequence shown in SEQ ID NO:78.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain containing the amino acid sequence shown in SEQ ID NO:80, and a light chain containing the amino acid sequence shown in SEQ ID NO:84.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain containing the amino acid sequence shown in SEQ ID NO:82, and a light chain containing the amino acid sequence shown in SEQ ID NO:84.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:80, and a light chain comprising the amino acid sequence shown in SEQ ID NO:86.
  • the anti-FGFR2IIIb antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:82, and a light chain comprising the amino acid sequence shown in SEQ ID NO:86.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:41 and a light chain of the amino acid sequence shown in SEQ ID NO:43.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:45 and a light chain of the amino acid sequence shown in SEQ ID NO:47.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:49 and a light chain of the amino acid sequence shown in SEQ ID NO:51.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:53 and a light chain of the amino acid sequence shown in SEQ ID NO:55.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:57 and a light chain of the amino acid sequence shown in SEQ ID NO:59.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:70 and a light chain of the amino acid sequence shown in SEQ ID NO:76.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:72 and a light chain of the amino acid sequence shown in SEQ ID NO:76.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:74 and a light chain of the amino acid sequence shown in SEQ ID NO:76.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:70 and a light chain of the amino acid sequence shown in SEQ ID NO:78.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:72 and a light chain of the amino acid sequence shown in SEQ ID NO:78.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:74 and a light chain of the amino acid sequence shown in SEQ ID NO:78.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:80 and a light chain of the amino acid sequence shown in SEQ ID NO:84.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:82 and a light chain of the amino acid sequence shown in SEQ ID NO:84.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:80 and a light chain of the amino acid sequence shown in SEQ ID NO:86.
  • the anti-FGFR2IIIb antibody comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:82 and a light chain of the amino acid sequence shown in SEQ ID NO:86.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:41, and the amino acid sequence of the light chain is shown in SEQ ID NO:43.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:45, and the amino acid sequence of the light chain is shown in SEQ ID NO:47.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:49, and the amino acid sequence of the light chain is shown in SEQ ID NO:51.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:53, and the amino acid sequence of the light chain is shown in SEQ ID NO:55.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:57, and the amino acid sequence of the light chain is shown in SEQ ID NO:59.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:70, and the amino acid sequence of the light chain is shown in SEQ ID NO:76.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:72, and the amino acid sequence of the light chain is shown in SEQ ID NO:76.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:74, and the amino acid sequence of the light chain is shown in SEQ ID NO:76.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:70, and the amino acid sequence of the light chain is shown in SEQ ID NO:78.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:72, and the amino acid sequence of the light chain is shown in SEQ ID NO:78.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:74, and the amino acid sequence of the light chain is shown in SEQ ID NO:78.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:80, and the amino acid sequence of the light chain is shown in SEQ ID NO:84.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:82, and the amino acid sequence of the light chain is shown in SEQ ID NO:84.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:80, and the amino acid sequence of the light chain is shown in SEQ ID NO:86.
  • amino acid sequence of the heavy chain of the anti-FGFR2IIIb antibody is shown in SEQ ID NO:82, and the amino acid sequence of the light chain is shown in SEQ ID NO:86.
  • anti-FGFR2IIIb antibodies involved here also include anti-FGFR2IIIb antibodies with the heavy chain C-terminal lysine deletion.
  • Tables S1 and S2 provide amino acid sequence information for the CDR and variable regions of some exemplary anti-FGFR2IIIb antibodies or their antigen-binding fragments (e.g., chimeric antibodies ch-Ab5, ch-Ab13, ch-Ab34, ch-Ab37, ch-Ab41 and humanized antibodies hzAb13-1.1, hzAb13-1.2, hzAb13-1.3, hzAb13-2.1, hzAb13-2.2, hzAb13-2.3, hzAb41-1.1, hzAb41-1.2, hzAb41-2.1, hzAb41-2.2).
  • some exemplary anti-FGFR2IIIb antibodies or their antigen-binding fragments e.g., chimeric antibodies ch-Ab5, ch-Ab13, ch-Ab34, ch-Ab37, ch-Ab41 and humanized antibodies hzAb13-1.1, hzAb13-1.2, hzAb13-1.3, hzAb
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment disclosed herein exhibits good antigen-binding activity. Any of the anti-FGFR2IIIb antibody or its antigen-binding fragment disclosed herein can bind to human FGFR2IIIb and/or monkey FGFR2IIIb.
  • any of the anti-FGFR2IIIb antibody or its antigen-binding fragment disclosed herein when measured by surface plasmon resonance (SPR) technology, can bind to human FGFR2IIIb at the following concentrations : 5.00E-08M or less, 2.00E-08M or less, 1.44E-08M or less, 1.36E-08M or less, 1.32E-08M or less, 1.31E-08M or less, 1.29E-08M or less, 1.00E-08M or less, 9.95E-09M or less, 9.15E-09M or less, 8.31E-08M or less.
  • SPR surface plasmon resonance
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment provided in this disclosure can inhibit or block the binding of FGFR2IIIb to FGF.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment provided in this disclosure can inhibit FGF-mediated FGFR2IIIb phosphorylation.
  • any of the anti-FGFR2IIIb antibody or its antigen-binding fragment provided in this disclosure can kill various tumor cells through ADCC.
  • the tumor is a tumor expressing FGFR2IIIb.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment of this disclosure is unfucosylated. Defucosylation can enhance the interaction between the anti-FGFR2IIIb antibody or its antigen-binding fragment and Fc ⁇ RIIIa, thereby enhancing the ADCC activity of the anti-FGFR2IIIb antibody or its antigen-binding fragment.
  • Methods for generating antibodies or their antigen-binding fragments with little or no fucose at the Fc glycosylation site without altering the amino acid sequence are known in the art, such as adjusting the composition of the culture medium in which the host cells expressing the antibody or its antigen-binding fragment are located, or knocking out fucose expression-related genes (such as the fut8 gene) in the host cells expressing the antibody or its antigen-binding fragment.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment provided in this disclosure can induce tumor growth regression in vivo.
  • the tumor is a tumor expressing FGFR2IIIb.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment provided in this disclosure can delay tumor growth in vivo.
  • the tumor is a tumor expressing FGFR2IIIb.
  • the disclosed anti-FGFR2IIIb antibody or its antigen-binding fragment has good safety profile.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment is a monoclonal antibody. In some embodiments, the anti-FGFR2IIIb antibody or its antigen-binding fragment is a monospecific antibody. In some embodiments, the anti-FGFR2IIIb antibody or its antigen-binding fragment is a multispecific antibody (e.g., a bispecific antibody, a trispecific antibody, etc.).
  • This disclosure provides isolated nucleic acids containing nucleotide sequences encoding the anti-FGFR2IIIb antibody or its antigen-binding fragment as described in this disclosure.
  • the sequence listing provides exemplary examples of nucleotide sequences encoding the anti-FGFR2IIIb antibody or its antigen-binding fragment.
  • the vector is a cloning vector.
  • the vector is an expression vector.
  • the expression vector is pcDNA3.1(+).
  • the expression vector may optionally be capable of expressing any expression vector of the anti-FGFR2IIIb antibody or its antigen-binding fragment described herein.
  • the host cell is a suitable host cell for cloning or expressing an anti-FGFR2IIIb antibody or its antigen-binding fragment.
  • the host cell is a prokaryotic cell.
  • the host cell is a eukaryotic cell.
  • the host cell is selected from yeast cells, mammalian cells, or other cells suitable for preparing an anti-FGFR2IIIb antibody or its antigen-binding fragment.
  • Mammalian cells include, for example, Chinese hamster ovary (CHO) cells and CHO-S cells.
  • this disclosure provides a fusion protein comprising the anti-FGFR2IIIb antibody of this disclosure or an antigen-binding fragment thereof.
  • ADCs Antibody-drug conjugates
  • antibody-drug conjugates comprising the anti-FGFR2IIIb antibody of this disclosure or its antigen-binding fragment.
  • the antibody-drug conjugate comprises the anti-FGFR2IIIb antibody or its antigen-binding fragment, and a cytotoxic drug.
  • This disclosure also provides an anti-FGFR2IIIb chimeric antigen receptor (CAR) comprising the anti-FGFR2IIIb antibody of this disclosure or its antigen-binding fragment.
  • CAR chimeric antigen receptor
  • Anti-FGFR2IIIb CARs may include (a) an extracellular antigen-binding domain containing FGFR2IIIb binding; (b) a transmembrane domain; and (c) an intracellular signal transduction domain.
  • the immune effector cells are T cells, NK cells, peripheral blood mononuclear cells (PBMCs), hematopoietic stem cells, pluripotent stem cells, or embryonic stem cells.
  • PBMCs peripheral blood mononuclear cells
  • compositions comprising the anti-FGFR2IIIb antibody of this disclosure or an antigen-binding fragment thereof, a fusion protein, an antibody-drug conjugate, or engineered immune effector cells.
  • the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients.
  • Pharmaceutically acceptable excipients include, for example, excipients, diluents, encapsulating materials, fillers, buffers, or other reagents.
  • the anti-FGFR2IIIb antibody or its antigen-binding fragment may be completely defucosylated (meaning it contains no detectable fucose) or partially defucosylated. In some embodiments, 20% or less, 18% or less, 16% or less, 14% or less, 12% or less, 10% or less, 8% or less, 6% or less, 5% or less, 3% or less, 2% or less, 1.5% or less, 1% or less, 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less, 0.2% or less, 0.1% or less, or 0% of the anti-FGFR2IIIb antibody or its antigen-binding fragment contains fucose.
  • 0 to 20%, 0 to 18%, 0 to 16%, 0 to 14%, 0 to 12%, 0 to 10%, 0 to 8%, 0 to 6%, 0 to 5%, 0 to 3%, 0 to 2%, 0 to 1.5%, 0 to 1%, 0 to 0.9%, 0 to 0.8%, 0 to 0.7%, 0 to 0.6%, 0 to 0.5%, 0 to 0.4%, 0 to 0.3%, 0 to 0.2%, or 0 to 0.1% of the anti-FGFR2IIIb antibody or its antigen-binding fragment contains fucose.
  • this disclosure provides a method for preparing an anti-FGFR2IIIb antibody or an antigen-binding fragment thereof, the method comprising: culturing host cells to express the anti-FGFR2IIIb antibody or the antigen-binding fragment thereof, and isolating and purifying the anti-FGFR2IIIb antibody or the antigen-binding fragment thereof in the system.
  • a nucleic acid encoding the anti-FGFR2IIIb antibody or the antigen-binding fragment thereof is isolated and inserted into one or more vectors for further cloning and/or expression in host cells.
  • the nucleic acid can be obtained using various methods well known in the art, such as gene splicing and chemical synthesis.
  • the purity of anti-FGFR2IIIb antibody or its antigen-binding fragment can be determined using any of a variety of well-known analytical methods, such as gel electrophoresis, high-performance liquid chromatography, size exclusion chromatography, etc.
  • the physicochemical properties and/or biological activities of the anti-FGFR2IIIb antibody or its antigen-binding fragment disclosed herein can be identified, screened or characterized by a variety of assay methods known in the art.
  • the anti-FGFR2IIIb antibody used may be ch-Ab5, ch-Ab13, ch-Ab34, ch-Ab37, ch-Ab41, hzAb13-1.1, hzAb13-1.2, hzAb13-1.3, hzAb13-2.1, hzAb13-2.2, hzAb13-2.3, hzAb41-1.1, hzAb41-1.2, hzAb41-2.1 and/or hzAb41-2.2.
  • This disclosure provides the use of the anti-FGFR2IIIb antibody or its antigen-binding fragment, the fusion protein, the antibody-drug conjugate, the engineered immune effector cells, or the pharmaceutical composition in the preparation of a medicament for treating diseases expressing FGFR2IIIb.
  • this disclosure also provides the use of the anti-FGFR2IIIb antibody or its antigen-binding fragment, the fusion protein, the antibody-drug conjugate, the engineered immune effector cells, or the pharmaceutical composition in combination with one or more additional therapeutic agents in the preparation of a medicament for treating diseases expressing FGFR2IIIb.
  • this disclosure also provides the use of the anti-FGFR2IIIb antibody or its antigen-binding fragment, the fusion protein, the antibody-drug conjugate, the engineered immune effector cells, or the pharmaceutical composition in the preparation of a medicament for treating diseases expressing FGFR2IIIb in combination with one or more additional therapeutic agents.
  • This disclosure provides a method for treating a disease expressing FGFR2IIIb, comprising administering to a subject the anti-FGFR2IIIb antibody or its antigen-binding fragment, the fusion protein, the antibody-drug conjugate, the engineered immune effector cells, or the pharmaceutical composition.
  • the method involves administering to a subject a therapeutically effective amount of the anti-FGFR2IIIb antibody or its antigen-binding fragment, the antibody-drug conjugate, the engineered immune effector cells, or the pharmaceutical composition to treat a disease expressing FGFR2IIIb.
  • the method includes further administering to the subject one or more additional therapeutic agents.
  • the disease is a tumor.
  • the tumor contains FGFR2 gene amplification.
  • the tumor overexpresses FGFR2IIIb.
  • the tumor overexpresses FGFR2IIIb but does not contain FGFR2 gene amplification.
  • the expression or overexpression of FGFR2IIIb is determined by immunohistochemistry (IHC).
  • the tumor is a non-solid tumor.
  • the tumor is a hematologic malignancy.
  • the tumor is a lymphoma, such as Hodgkin's lymphoma, non-Hodgkin's lymphoma, or B-cell lymphoma.
  • the tumor is leukemia.
  • the tumor is multiple myeloma.
  • the tumor is a solid tumor.
  • the tumor is lung cancer (including non-small cell lung cancer), breast cancer, endometrial cancer, prostate cancer, cervical cancer, urothelial carcinoma, pancreatic cancer, colorectal cancer, melanoma, liver cancer (including hepatocellular carcinoma), ovarian cancer, bladder cancer, gastric cancer, esophageal cancer, gastroesophageal junction (GEJ) cancer, kidney cancer (including renal cell carcinoma), bile duct cancer, head and neck cancer, and/or glioma.
  • lung cancer including non-small cell lung cancer
  • breast cancer endometrial cancer
  • prostate cancer cervical cancer
  • pancreatic cancer pancreatic cancer
  • colorectal cancer melanoma
  • liver cancer including hepatocellular carcinoma
  • ovarian cancer bladder cancer
  • gastric cancer esophageal cancer
  • GEJ gastroesophageal junction
  • kidney cancer including renal cell carcinoma
  • bile duct cancer including head and neck cancer
  • glioma glioma
  • the additional therapeutic agent in the above uses and methods can be a known oncology therapeutic agent.
  • oncology therapeutic agents include immune checkpoint inhibitors (e.g., anti-PD-1 antibodies or their antigen-binding fragments, anti-PD-L1 antibodies or their antigen-binding fragments), platinum-based agents (e.g., cisplatin, oxaliplatin, and carboplatin), taxanes (e.g., paclitaxel, albumin-bound paclitaxel, docetaxel, cabazitaxel), gemcitabine, capecitabine, enoxacin, epirubicin, FOLFOX (e.g., FOLFOX4, FOLFOX6, mFOLFOX6, FOLFOX7), FOLFIRI, leucovorin, 5-FU, mitomycin, and doxorubicin hydrochloride; wherein the FOLFOX is a combination of oxaliplatin, fluorouracil (5
  • kits comprising the anti-FGFR2IIIb antibody of this disclosure or its antigen-binding fragment, fusion protein, antibody-drug conjugate, engineered immune effector cells, or pharmaceutical composition.
  • the kit may be used for purposes such as implementing the anti-FGFR2IIIb antibody of this disclosure or its antigen-binding fragment, fusion protein, antibody-drug conjugate, engineered immune effector cells, or pharmaceutical composition, or for other uses.
  • the kit may include the anti-FGFR2IIIb antibody of this disclosure or its antigen-binding fragment, fusion protein, antibody-drug conjugate, engineered immune effector cells, or pharmaceutical composition, and reagents for detecting the presence of FGFR2IIIb in a biological sample.
  • the kit may also include instructions for use.
  • the kit may also include other materials required from a commercial and user perspective, such as other buffers, diluents, needles, syringes, etc.
  • An anti-FGFR2IIIb antibody or its antigen-binding fragment comprising: HCDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, 9, 17, 25 or 33; HCDR2 comprising the amino acid sequence shown in SEQ ID NO: 2, 10, 18, 26 or 34; HCDR3 comprising the amino acid sequence shown in SEQ ID NO: 3, 11, 19, 27 or 35; LCDR1 comprising the amino acid sequence shown in SEQ ID NO: 4, 12, 20, 28 or 36; LCDR2 comprising the amino acid sequence shown in SEQ ID NO: 5, 13, 21, 29 or 37; and LCDR3 comprising the amino acid sequence shown in SEQ ID NO: 6, 14, 22, 30 or 38.
  • HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6;
  • HCDR1 containing the amino acid sequence shown in SEQ ID NO:33 HCDR2 containing the amino acid sequence shown in SEQ ID NO:34
  • HCDR3 containing the amino acid sequence shown in SEQ ID NO:35 LCDR1 containing the amino acid sequence shown in SEQ ID NO:36
  • LCDR2 containing the amino acid sequence shown in SEQ ID NO:37 HCDR3 containing the amino acid sequence shown in SEQ ID NO:38.
  • An anti-FGFR2IIIb antibody or an antigen-binding fragment thereof comprising: HCDR1, HCDR2, and HCDR3 in a heavy chain variable region as shown in SEQ ID NO: 7, 15, 23, 31, 39, 61, 62, 63, 66, 67, 96, or 98, and LCDR1, LCDR2, and LCDR3 in a light chain variable region as shown in SEQ ID NO: 8, 16, 24, 32, 40, 64, 65, 68, 69, 97, or 99, wherein the CDRs are defined according to Kabat, IMGT, Chothia, Contact, AbM, and/or CCG.
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:7, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:8;
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:39, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:40;
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:61, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:64;
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:62, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:64;
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:63, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:64;
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:66, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:68;
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:67, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:69;
  • HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:96, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO:97; or
  • HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO:98, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO:99;
  • the CDR is defined according to Kabat, IMGT, Chothia, Contact, AbM and/or CCG.
  • Implementation Scheme 5 An anti-FGFR2IIIb antibody or antigen-binding fragment thereof according to any one of Implementation Schemes 1-4, wherein the anti-FGFR2IIIb antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 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: 7, 15, 23, 31, 39, 61, 62, 63, 66, 67, 96, or 98.
  • Implementation Scheme 6 An anti-FGFR2IIIb antibody or antigen-binding fragment thereof according to any one of Implementation Schemes 1-5, wherein the anti-FGFR2IIIb antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence identity of at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence shown in SEQ ID NO: 8, 16, 24, 32, 40, 64, 65, 68, 69, 97, or 99.
  • a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence shown in SEQ ID NO:7, and a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence shown in SEQ ID NO:8;
  • a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO:15, and a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO:16;
  • a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO:23, and a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO:24;
  • a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO:31, and a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO:32;
  • a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO: 63, and a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO: 65;
  • a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO:66, and a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO:68;
  • a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO: 67, and a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO: 68;
  • a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO: 66, and a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO: 69;
  • a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO: 67, and a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO: 69;
  • a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO: 96, and a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO: 97; or
  • a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO: 98, and a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence shown in SEQ ID NO: 99.
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:7 and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:8;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:23, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:24;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:31, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:32;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:39, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:40;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:64;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:62, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:64;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:63, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:64;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:65;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:62, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:65;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:63, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:65;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:66, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:68;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:67, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:68;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:66, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:69;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:67, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:69;
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:96, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:97; or
  • a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:98 and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:99.
  • Implementation Scheme 9 An anti-FGFR2IIIb antibody or its antigen-binding fragment according to any one of Implementation Schemes 1-8, wherein the antigen-binding fragment is a Fab fragment, an F(ab') 2 fragment, an Fd fragment, an Fv fragment, a separated CDR region, or a scFv.
  • Implementation Scheme 10 An anti-FGFR2IIIb antibody or antigen-binding fragment thereof according to any one of Implementation Schemes 1-9, wherein the anti-FGFR2IIIb antibody or antigen-binding fragment thereof is murine, chimeric, or humanized.
  • Implementation Scheme 12 An anti-FGFR2IIIb antibody or an antigen-binding fragment thereof according to any one of Implementation Schemes 1-11, wherein the anti-FGFR2IIIb antibody comprises a heavy chain having an amino acid sequence that is at least 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: 41, 45, 49, 53, 57, 70, 72, 74, 80, or 82.
  • Implementation Scheme 13 An anti-FGFR2IIIb antibody or an antigen-binding fragment thereof according to any one of Implementation Schemes 1-12, wherein the anti-FGFR2IIIb antibody comprises a light chain having an amino acid sequence that is at least 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: 43, 47, 51, 55, 59, 76, 78, 84, or 86.
  • An anti-FGFR2IIIb antibody or an antigen-binding fragment thereof, wherein the anti-FGFR2IIIb antibody comprises:
  • a heavy chain comprising the amino acid sequence shown in SEQ ID NO:70, and a light chain comprising the amino acid sequence shown in SEQ ID NO:76;
  • a heavy chain comprising the amino acid sequence shown in SEQ ID NO:70, and a light chain comprising the amino acid sequence shown in SEQ ID NO:78;
  • a heavy chain comprising the amino acid sequence shown in SEQ ID NO:72, and a light chain comprising the amino acid sequence shown in SEQ ID NO:78;
  • a heavy chain comprising the amino acid sequence shown in SEQ ID NO:74, and a light chain comprising the amino acid sequence shown in SEQ ID NO:78;
  • a heavy chain comprising the amino acid sequence shown in SEQ ID NO:80, and a light chain comprising the amino acid sequence shown in SEQ ID NO:84;
  • a heavy chain comprising the amino acid sequence shown in SEQ ID NO:82, and a light chain comprising the amino acid sequence shown in SEQ ID NO:84;
  • a heavy chain comprising the amino acid sequence shown in SEQ ID NO:80, and a light chain comprising the amino acid sequence shown in SEQ ID NO:86; or
  • a heavy chain comprising the amino acid sequence shown in SEQ ID NO:82, and a light chain comprising the amino acid sequence shown in SEQ ID NO:86.
  • Binding to human FGFR2IIIb preferably, measured by surface plasmon resonance technology, with KD of 5E-08M or less, 1E-09M or less, or 5E-10M or less binding to human FGFR2IIIb;
  • Implementation Scheme 18 An anti-FGFR2IIIb antibody or its antigen-binding fragment according to any one of Implementation Schemes 1-17, wherein the anti-FGFR2IIIb antibody or its antigen-binding fragment is a monospecific antibody or a multispecific antibody.
  • Implementation Scheme 19 An isolated nucleic acid comprising a nucleotide sequence encoding an anti-FGFR2IIIb antibody or an antigen-binding fragment thereof as described in any one of Implementation Schemes 1-18.
  • Implementation Scheme 20 A carrier comprising the nucleic acid described in Implementation Scheme 19.
  • Implementation Scheme 21 A host cell comprising the nucleic acid described in Implementation Scheme 19, or the vector described in Implementation Scheme 20.
  • Implementation Scheme 22 A method for preparing an anti-FGFR2IIIb antibody or an antigen-binding fragment thereof as described in any one of Implementation Schemes 1-18, comprising culturing the host cells described in Implementation Scheme 21 to express the anti-FGFR2IIIb antibody or the antigen-binding fragment thereof, and isolating and purifying the anti-FGFR2IIIb antibody or the antigen-binding fragment thereof in the system.
  • Implementation Scheme 23 A fusion protein comprising any one of the anti-FGFR2IIIb antibody or its antigen-binding fragment as described in Implementation Schemes 1-18.
  • Implementation Scheme 25 A chimeric antigen receptor comprising an anti-FGFR2IIIb antibody or an antigen-binding fragment thereof, as described in any one of Implementation Schemes 1-18.
  • Implementation Scheme 27 A pharmaceutical composition comprising an anti-FGFR2IIIb antibody or an antigen-binding fragment thereof according to any one of Implementation Schemes 1-18, a fusion protein according to Implementation Scheme 23, an antibody-drug conjugate according to Implementation Scheme 24, or an engineered immune effector cell according to Implementation Scheme 26; optionally, the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients.
  • Implementation Scheme 28 Use of the anti-FGFR2IIIb antibody or antigen-binding fragment thereof according to any one of Implementation Schemes 1-18, the fusion protein according to Implementation Scheme 23, the antibody-drug conjugate according to Implementation Scheme 24, the engineered immune effector cells according to Implementation Scheme 26, or the pharmaceutical composition according to Implementation Scheme 27 in the preparation of a medicament for treating diseases expressing FGFR2IIIb.
  • Implementation Scheme 29 Use of any anti-FGFR2IIIb antibody or antigen-binding fragment thereof according to any one of Implementation Schemes 1-18, the fusion protein according to Implementation Scheme 23, the antibody-drug conjugate according to Implementation Scheme 24, the engineered immune effector cells according to Implementation Scheme 26, or the pharmaceutical composition according to Implementation Scheme 27, together with one or more additional therapeutic agents, in the preparation of a medicament for treating diseases expressing FGFR2IIIb.
  • Implementation Scheme 32 The use according to any one of Implementation Schemes 29-31, wherein the additional therapeutic agent is an immune checkpoint inhibitor or FOLFOX, preferably an anti-PD-1 antibody or its antigen-binding fragment, an anti-PD-L1 antibody or its antigen-binding fragment, or mFOLFOX6.
  • the additional therapeutic agent is an immune checkpoint inhibitor or FOLFOX, preferably an anti-PD-1 antibody or its antigen-binding fragment, an anti-PD-L1 antibody or its antigen-binding fragment, or mFOLFOX6.
  • Implementation Scheme 33 The use according to any one of Implementation Schemes 30-32, wherein the tumor is a hematologic malignancy, lung cancer, breast cancer, endometrial cancer, prostate cancer, cervical cancer, urothelial carcinoma, pancreatic cancer, colorectal cancer, melanoma, liver cancer, ovarian cancer, bladder cancer, gastric cancer, esophageal cancer, gastroesophageal junction cancer, kidney cancer, bile duct cancer, head and neck cancer, and/or glioma.
  • the tumor is a hematologic malignancy, lung cancer, breast cancer, endometrial cancer, prostate cancer, cervical cancer, urothelial carcinoma, pancreatic cancer, colorectal cancer, melanoma, liver cancer, ovarian cancer, bladder cancer, gastric cancer, esophageal cancer, gastroesophageal junction cancer, kidney cancer, bile duct cancer, head and neck cancer, and/or glioma.
  • Implementation scheme 36 The use described in implementation scheme 34 or 35, wherein the tumor does not contain FGFR2 gene amplification.
  • Implementation Scheme 37 The use according to any one of Implementation Schemes 30-35, wherein the tumor comprises an amplified FGFR2 gene.
  • Implementation Scheme 38 A method for treating a disease expressing FGFR2IIIb, comprising administering to a subject an anti-FGFR2IIIb antibody or an antigen-binding fragment thereof as described in any one of Implementation Schemes 1-18, a fusion protein as described in Implementation Scheme 23, an antibody-drug conjugate as described in Implementation Scheme 24, engineered immune effector cells as described in Implementation Scheme 26, or a pharmaceutical composition as described in Implementation Scheme 27.
  • Implementation Scheme 39 The method according to Implementation Scheme 38, wherein the method includes further administering one or more additional therapeutic agents to the subject.
  • Implementation Scheme 40 The method according to Implementation Scheme 38 or 39, wherein the disease is a tumor.
  • Implementation Scheme 42 The method according to any one of Implementation Schemes 39-41, wherein the additional therapeutic agent is an immune checkpoint inhibitor or FOLFOX, preferably an anti-PD-1 antibody or its antigen-binding fragment, an anti-PD-L1 antibody or its antigen-binding fragment, or mFOLFOX6.
  • the additional therapeutic agent is an immune checkpoint inhibitor or FOLFOX, preferably an anti-PD-1 antibody or its antigen-binding fragment, an anti-PD-L1 antibody or its antigen-binding fragment, or mFOLFOX6.
  • Implementation Scheme 43 The method according to any one of Implementation Schemes 40-42, wherein the tumor is a hematologic malignancy, lung cancer, breast cancer, endometrial cancer, prostate cancer, cervical cancer, urothelial carcinoma, pancreatic cancer, colorectal cancer, melanoma, liver cancer, ovarian cancer, bladder cancer, gastric cancer, esophageal cancer, gastroesophageal junction cancer, kidney cancer, bile duct cancer, head and neck cancer, and/or glioma.
  • the tumor is a hematologic malignancy, lung cancer, breast cancer, endometrial cancer, prostate cancer, cervical cancer, urothelial carcinoma, pancreatic cancer, colorectal cancer, melanoma, liver cancer, ovarian cancer, bladder cancer, gastric cancer, esophageal cancer, gastroesophageal junction cancer, kidney cancer, bile duct cancer, head and neck cancer, and/or glioma.
  • Implementation Scheme 48 A kit comprising the anti-FGFR2IIIb antibody or its antigen-binding fragment as described in any one of Implementation Schemes 1-18, the fusion protein as described in Implementation Scheme 23, the antibody-drug conjugate as described in Implementation Scheme 24, the engineered immune effector cells as described in Implementation Scheme 26, or the pharmaceutical composition as described in Implementation Scheme 27.
  • DNA sequences encoding the full-length open reading frames (amino acid sequences as shown in SEQ ID NO: 92, 93, and 94, respectively) of human FGFR2IIIb, human FGFR2IIIc, and human FGFR2IIIb (S252W) were subcloned into the expression vector pcDNATM3.1/Zeo(+) (Invitrogen catalog number: V86020).
  • HEK-293T cells were transfected with Lipofectamine 3000 (Gibco, catalog number: L3000001) transfection reagent. After bleomycin selection for 2-3 weeks, the cells were further divided using the limiting dilution method.
  • Monoclonal cells were obtained, and the expression levels of human FGFR2IIIb, human FGFR2IIIc, and human FGFR2IIIb (S252W) on the surface of the monoclonal cell line HEK-293T were detected by flow cytometry (FACS).
  • Monoclonal cell lines with high expression levels of human FGFR2IIIb, human FGFR2IIIc, and human FGFR2IIIb (S252W) were selected and named HEK293T-hFGFR2IIIb cells, HEK293T-hFGFR2IIIc cells, and HEK293T-hFGFR2IIIb (S252W) cells, respectively.
  • the DNA sequence encoding the open reading frame of the extracellular domain of human FGFR2IIIb protein (Uniprot: P21802-3) was fused with the DNA sequence of human IgG1 Fc tag and cloned into the expression vector pcDNA3.1(+) (Invitrogen, catalog number: V-79020).
  • the expression vector was transfected into Expi293F cells for transient expression, and the fusion protein human FGFR2IIIb-Fc Tag (amino acid sequence as shown in SEQ ID NO: 95) was obtained by purification using a protein A column (GE Healthcare).
  • human FGFR2IIIb-Fc Tag was emulsified with Freund's complete adjuvant (for initial immunization) or Freund's incomplete adjuvant (for booster immunization) at a volume ratio of 1:1.
  • BALB/c and A/J mice were subcutaneously immunized at 100 ⁇ g/mouse every 2 weeks for 4 immunizations over 6 weeks. Serum was collected after the 3rd and 4th immunizations, and antibody titers were measured by ELISA. Three days prior to cell fusion, mice were sprint-immunized by intravenous injection of adjuvant-free human FGFR2IIIb-Fc Tag.
  • Spleen cells (approximately 1 ⁇ 108 cells) from immunized mice were fused with SP2/0-Ag14 myeloma cells (1 ⁇ 107 to 3 ⁇ 107 cells) using an electrofusion instrument (BTX, model: ECM2001). After fusion, the fused cells were diluted with 500 mL of RPMI-1640 medium containing 10% fetal bovine serum, and then aliquoted into 96-well plates at 0.1 mL/well. The plates were incubated at 37°C in a 5% CO2 incubator.
  • Positive clones were screened using a protein- and cell-based binding and ligand competition assay. Positive hybridoma cells in logarithmic growth were counted and diluted to 5-10 cells/mL with complete RPMI-1640 medium (containing 10% fetal bovine serum and 2% HT supplement, Sigma, HO137). Cells were seeded at 200 ⁇ L/well in 96-well plates and incubated at 37°C with 5% CO2 for approximately 8 days. The supernatant from each visible monoclonal cell well was collected for further screening to obtain positive monoclonal cells.
  • complete RPMI-1640 medium containing 10% fetal bovine serum and 2% HT supplement, Sigma, HO137
  • Example 4 cDNA acquisition and chimeric antibody construction of anti-FGFR2IIIb antibody
  • RNA was isolated from positive monoclonal cells producing anti-human FGFR2IIIb antibody using the RNeasy mini kit (Qiagen, catalog number: 74104) as a template, and first-strand cDNA was synthesized using the PrimeScript 1st strand cDNA Synthesis Kit (TAKARA, catalog number: D6110A). Then, using the first-strand cDNA as a template, PCR was performed with degenerate mouse IgG primers to obtain a PCR mixture. The PCR mixture was separated by electrophoresis on a 1% agarose/Tris-borate gel containing 0.5 ⁇ g/mL ethidium bromide.
  • DNA fragments of the expected size were excised from the gel and purified.
  • 3 ⁇ L of the purified PCR product was cloned into the pMD-18T vector (Takara, catalog number: D101A) and transformed into One Shot TOP10 chemically competent *E. coli* (Invitrogen, catalog number: C4040-03) for culture. Single colonies were selected for DNA sequencing, yielding the heavy chain variable region (VH) and light chain variable region (VL) sequences of five murine monoclonal antibodies (Ab5, Ab13, Ab34, Ab37, and Ab41).
  • a chimeric light chain was constructed by linking the VL region gene synthesis fragment of mouse antibody to the constant region of human ⁇ chain, and a chimeric heavy chain was constructed by linking the VH region gene synthesis fragment of mouse antibody to the constant region of human IgG1.
  • Expression plasmids containing chimeric light chain DNA and chimeric heavy chain DNA were transfected into FUT8 knockout CHO-S cells (100 mL, at a cell density of 6.3 ⁇ 106 /mL) for transient expression, and then cultured in CHOgro Expression medium (Mirus Bio, catalog number: 6200A) at 32°C for 10–12 days on a shaker.
  • the chimeric antibody in the supernatant was purified using a protein A column (GE Healthcare). The sequence information of the chimeric antibody is shown in Table 1 below.
  • Bayer's Aprutumab (the amino acid sequences of the heavy and light chains are shown in SEQ ID NO: 88 and 89, respectively, specifically recognizing and binding to FGFR2 antigen, including FGFR2b) and Amgen's Bemarituzumab (the amino acid sequences of the heavy and light chains are shown in SEQ ID NO: 90 and 91, respectively, specifically recognizing and binding to FGFR2b antigen) were selected as benchmarks to evaluate the antigen-binding activity of the chimeric antibodies.
  • the preparation of Aprutumab and Bemarituzumab followed the method described in Example 4.
  • Human FGFR2IIIb-His protein (Sino Biological, catalog number: 16485-H08H) was diluted to 2 ⁇ g/mL with pH 7.4 PBS (SmartBuffer, catalog number: PBS-2050) buffer and added to a 96-well plate (Costar, catalog number: 9018) at a volume of 100 ⁇ L/well, and incubated overnight at 4°C for 16 h. After discarding the liquid, add 300 ⁇ L of 2% BSA (SIGMA, catalog number: B2064-100G) diluted in PBS to each well for blocking, and incubate at 37°C for 2 hours.
  • pH 7.4 PBS SmartBuffer, catalog number: PBS-2050
  • PBST buffer PBS containing 0.05% Tween-20, pH 7.4. Then, add 100 ⁇ L of serially diluted (0.001-100 nM) anti-FGFR2IIIb chimeric antibody, reference, or hIgG1 control antibody to each well, and incubate at 37°C for 1 hour. After incubation, wash the plate three times with PBST, and add 100 ⁇ L of 1:5000 diluted horseradish peroxidase (HRP)-conjugated goat anti-human IgG (H+L) (Jackson Immuno Research, catalog number: 109-035-098) to each well, and incubate at 37°C for 1 hour.
  • HRP horseradish peroxidase
  • H+L horseradish peroxidase
  • TMB chromogenic substrate TIANGEN, catalog number: PA107-01
  • 100 ⁇ L of TMB chromogenic substrate TIANGEN, catalog number: PA107-01
  • the reaction was then stopped by adding 50 ⁇ L of 1M H2SO4 to each well.
  • the absorbance was measured using a microplate reader (Teken, Infinite F50) at a wavelength of 450 nm (reference wavelength: 620 nm).
  • the antibody-antigen binding curve was fitted, and the EC50 was calculated.
  • Figure 1 and Table 2 The results show that all the chimeric antibodies specifically bound the FGFR2IIIb antigen, and the EC50 values were comparable to those of Aprutumab and Bemarituzumab, reaching as low as E-11M.
  • Humanization of ch-AB13 and ch-Ab41 was performed using the CDR transplantation method (see, for example, US Patent No. 5,225,539). Humanization of ch-Ab13 yielded three heavy chain variable regions (amino acid sequences shown in SEQ ID NO: 61-63, respectively) and two light chain variable regions (amino acid sequences shown in SEQ ID NO: 64 and 65, respectively). Humanization of ch-Ab41 yielded two heavy chain variable regions (amino acid sequences shown in SEQ ID NO: 66 and 67, respectively) and two light chain variable regions (amino acid sequences shown in SEQ ID NO: 68 and 69, respectively).
  • the humanized VH region was ligated to the human IgG1 constant region to construct the humanized heavy chain, and the humanized VL region was ligated to the human ⁇ chain constant region to construct the humanized light chain.
  • the humanized antibody was constructed, expressed, and purified according to the method in Example 4. The sequence information of the anti-FGFR2IIIb humanized antibody is shown in Table 3.
  • Aprutumab and Bemarituzumab were selected as reference standards.
  • Surface plasmon resonance (SPR) technology was used to detect the affinity of anti-FGFR2IIIb antibody for human FGFR2IIIb-His protein; the preparation of aprutumab was as described in Example 4.
  • Antibodies were captured using a CM5 (Cytiva, catalog number 29127556) biosensor chip coupled with Protein A.
  • the antigen, human FGFR2IIIb-His protein (Sino Biological, catalog number: 16485-H08H), was then passed through the chip surface. Binding and dissociation curves were obtained by real-time detection of the reaction signal using a Biacore 8K instrument.
  • Biacore 8KControl Software 3.0 was used to acquire binding and dissociation curves in real time, and Biacore Insight Evaluation Software 3.0 was used for data analysis. After double subtraction (i.e., the experimental channel signal was subtracted from the control channel signal in each cycle, and the sample signal was subtracted from the blank signal), the data were fitted using a Langmuir 1:1 model to calculate the binding rate constant ka , dissociation rate constant kd , and equilibrium constant KD . The results are shown in Table 4. The results show that the affinity of the humanized antibodies ch-Ab13 and ch-Ab41 for human FGFR2IIIb is comparable to that of their parental chimeric antibodies, and is superior to or comparable to the reference standard.
  • Example 8 Cell binding assay of anti-FGFR2IIIb antibody
  • the EC50 values of their in vitro binding with all tested cell lines were comparable to those of the Bemarituzumab reference.
  • Example 9 Blocking analysis of ligand/receptor binding by anti-FGFR2IIIb antibody
  • Flow cytometry was used to analyze the blocking activity of anti-FGFR2IIIb antibody against the binding of ligands to cells expressing human FGFR2IIIb.
  • KATOIII cells naturally expressing FGFR2IIIb were prepared into a cell suspension with a density of 0.5 ⁇ 106 - 1 ⁇ 106 /mL using FACS buffer (Miltenyi Biotec, catalog number: 130-091-221).
  • FGF2-biotin is from ACRO Biosystems, catalog number FGC-H81E3, working concentration 0.1 ⁇ g/mL
  • FGF7-biotin is from ACRO Biosystems, catalog number FG7-H82E7, working concentration 0.2 ⁇ g/mL
  • FGF10-biotin is from ACRO Biosystems, catalog number FG0-H81Q7, working concentration 0.1 ⁇ g/mL
  • incubate at 4°C for 30 minutes.
  • Blocking rate (%) (1 - experimental group MFI / hIgG1 group MFI) ⁇ 100%.
  • FGFR1IIIb-His (Sino Biological, catalog number 16482-H08H), FGFR3IIIb-His (Sino Biological, catalog number 16486-H08H), or FGFR4-His (Sino Biological, catalog number 10538-H08H) proteins were diluted to 2 ⁇ g/mL using PBS (SmartBuffer, catalog number: PBS-2050) at pH 7.4. 100 ⁇ L of each protein was added to a 96-well plate (Costar, catalog number: 9018) and incubated overnight at 4°C for 16 h.
  • PBS SmartBuffer, catalog number: PBS-2050
  • HEK293T-hFGFR2IIIc cells were prepared into a cell suspension with a density of 0.5 ⁇ 106 - 1 ⁇ 106 /mL using FACS buffer (Miltenyi Biotec, catalog number: 130-091-221). 100 ⁇ L/well was added to each well of a 96-well plate (Corning, catalog number: 3894). Then, 100 ⁇ L of different concentrations (0.002-200 nM) of anti-FGFR2IIIb antibody, aprutumab, or bemarituzumab diluted with FACS buffer was added to each well, and the plates were incubated at 4°C in the dark for 1 hour.
  • Example 11 Anti-FGFR2IIIb antibody inhibits FGF1, FGF7, and FGF10-mediated FGFR2IIIb phosphorylation.
  • the Phospho-FGFR2 alpha DuoSet IC ELISA kit (R&D Systems, #DYC684E) was used with the SNU-16 cell line expressing FGFR2IIIb to investigate the inhibitory effect of anti-FGFR2IIIb antibody on FGF1, FGF7, and FGF10-mediated FGFR2IIIb phosphorylation.
  • SNU-16 cells were adjusted to a cell density of 2 ⁇ 105 /mL using RPMI-1640 basal medium containing 10% FBS, and seeded at 50 ⁇ L/well in 96-well plates.
  • test antibody at a concentration of 20 ⁇ g/mL was added, and the plates were incubated overnight at 37°C and 5% CO2 .
  • 50 ng/mL FGF1 (Sino Biological, catalog number 10013-HNAE)
  • 50 ng/mL FGF7 (Sino Biological, catalog number 10210-H07E)
  • 50 ng/mL FGF10 (Sino Biological, catalog number 10573-HNAE) solutions were prepared using RPMI-1640 basal medium containing 10% FBS.
  • a 96-well cell culture plate was taken out, and 100 ⁇ L of each of the 50 ng/mL FGF1, 50 ng/mL FGF7, or 50 ng/mL FGF10 solutions was added to each well. Untreated cells (without antibody and FGF) were set up as a blank control, and the cells were incubated at 37°C for 15 min. Afterwards, the 96-well cell culture plates were centrifuged, the supernatant was discarded, and 200 ⁇ L of cell lysis buffer was added to each well. The plates were then incubated on ice for 15 min, centrifuged at 2000 g/min for 5 min, and the supernatant was collected.
  • the phosphorylation level of FGFR2IIIb was detected by ELISA, following the instructions for the Phospho-FGFR2 alpha DuoSet IC ELISA kit. The results are shown in Figures 5A-5F. At a concentration of 10 ⁇ g/mL, ch-Ab13 and its humanized antibody, as well as ch-Ab41 and its humanized antibody, effectively inhibited the phosphorylation level of FGFR2IIIb by FGF1, FGF7, or FGF10 to the level of the blank control group, or even lower.
  • the ADCC activity of anti-FGFR2IIIb antibody was detected using KATOIII and SNU-16 cells as target cells and PBMCs as effector cells. Bemarituzumab was used as a reference, and hIgG1 was used as a negative control antibody.
  • KATOIII and SNU-16 cells were diluted to 3 ⁇ 105 cells/mL using culture medium, and each cell suspension was aliquoted into 96-well plates at 50 ⁇ L/well. Different concentrations of the test antibody were then added to the wells of the 96-well plates to achieve final concentrations of 5000 ng/mL, 500 ng/mL, 50 ng/mL, 5 ng/mL, 0.5 ng/mL, 0.05 ng/mL, and 0.005 ng/mL, respectively.
  • PBMC cells were resuscitated, and 100 ⁇ L of PBMC cell suspension (cell density 1.5 ⁇ 106 cells/mL) was added to each well of the 96-well plate at an effector cell:target cell ratio of 10:1. The cells were centrifuged at low speed to ensure thorough mixing and contact between effector and target cells, and incubated at 37°C in a 5% CO2 incubator for 18 hours. Add 20 ⁇ L of cell lysis buffer per well to the lysis buffer group (containing only culture medium and lysis buffer) and the maximum release group (containing target cells, culture medium, and lysis buffer). Incubate at 37°C in a 5% CO2 incubator for 45 min.
  • the ADCC activity of the anti-FGFR2IIIb antibody hzAb13-2.1 is comparable to that of Bemarituzumab.
  • Example 13 Pharmacodynamic evaluation of anti-FGFR2IIIb humanized antibody in SNU-16 human gastric cancer CB17-SCID mouse xenograft model
  • SNU-16 cells (source: Nanjing Kebai) were subcutaneously inoculated in the right axilla of SPF-grade female nude mice (source: Shanghai Lingchang), at a dose of 5 ⁇ 106 cells/mouse.
  • the animals were divided into 5 groups: solvent control group, Bemarituzumab group, hzAb13-1.2 group, hzAb13-2.1 group, and hzAb41-2.2 group, with 6 mice in each group.
  • Day 0 Day 0 (D0) was designated as the day of grouping.
  • the treatment group received an intravenous injection (i.v.) of the drug (2 mg/kg) once, while the solvent control group received an intravenous injection of PBS (pH 7.4).
  • Tumor volume was measured 2-3 times per week, and mouse weight was recorded. General mouse behavior was observed and recorded daily.
  • tumors were removed, weighed, and photographed.
  • the detection indicators and calculation formulas are as follows:
  • Tumor volume, TV (mm 3 ) 1/2 ⁇ (a ⁇ b 2 ); where a is the long diameter of the tumor and b is the short diameter of the tumor.
  • Relative tumor volume TVt / TV0 ; where TV0 is the tumor volume on day 0, and TVt is the tumor volume at each measurement.
  • T/C (%) TRTV / CRTV ⁇ 100%; where TRTV is the RTV of the treatment group and CRTV is the RTV of the solvent control group.
  • TGI(%) (1-TW/ TW0 ) ⁇ 100%; where TW is the tumor weight in the treatment group and TW0 is the tumor weight in the solvent control group.
  • WCR(%) (Wt t - Wt 0 )/Wt 0 ⁇ 100%; where Wt 0 is the body weight of the mouse on day 0, and Wt t is the body weight of the mouse at each measurement.
  • Table 8 Effects of anti-FGFR2IIIb antibody on SNU-16 human gastric cancer xenografts in mice. The p-value is compared with the blank control group.
  • Example 14 Pharmacodynamic evaluation of anti-FGFR2IIIb humanized antibody in JIMT-1 human breast cancer xenograft model in nude mice
  • SPF-grade female nude mice (source: Changzhou Cavens) were subcutaneously inoculated with JIMT-1 cells (low expression of FGFR2IIIb, source: AddexBio) in the right axilla at a dose of 2 ⁇ 106 cells/mouse.
  • the animals were divided into 5 groups of 6 mice each; the day of grouping was designated as day 0 (D0). Specific grouping and drug administration regimens are shown in Table 9.
  • Tumor volume was measured 2-3 times per week, and mouse weight was recorded. The general performance of the mice was observed and recorded daily. After the experiment, the tumor was removed, weighed, and photographed.
  • the detection indicators and calculation formulas are as follows:
  • Tumor volume, TV (mm 3 ) 1/2 ⁇ (a ⁇ b 2 ); where a is the long diameter of the tumor and b is the short diameter of the tumor.
  • Relative tumor volume TVt / TV0 ; where TV0 is the tumor volume on day 0, and TVt is the tumor volume at each measurement.
  • T/C (%) TRTV / CRTV ⁇ 100%; where TRTV is the RTV of the treatment group and CRTV is the RTV of the solvent control group.
  • TGI(%) (1-TW/ TW0 ) ⁇ 100%; where TW is the tumor weight in the treatment group and TW0 is the tumor weight in the solvent control group.
  • WCR(%) (Wt t - Wt 0 )/Wt 0 ⁇ 100%; where Wt 0 is the body weight of the mouse on day 0, and Wt t is the body weight of the mouse at each measurement.

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Abstract

L'invention concerne un anticorps ciblant le récepteur 2IIb de facteur de croissance des fibroblastes et son utilisation. L'invention concerne en outre une composition pharmaceutique contenant l'anticorps et son utilisation. L'anticorps peut être utilisé dans le traitement de tumeurs.
PCT/CN2025/093309 2024-05-09 2025-05-08 Anticorps ciblant le récepteur 2iib du facteur de croissance des fibroblastes et son utilisation Pending WO2025232811A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100196364A1 (en) * 2008-11-07 2010-08-05 Galaxy Biotech, Llc Monoclonal antibodies to fibroblast growth factor receptor 2
CN104066750A (zh) * 2011-11-23 2014-09-24 拜耳知识产权有限责任公司 抗fgfr2的抗体及其用途
CN104334724A (zh) * 2012-04-09 2015-02-04 第一三共株式会社 抗-fgfr2抗体
US20160317656A1 (en) * 2013-10-08 2016-11-03 Daiichi Sankyo Company, Limited Combination of anti-fgfr2 antibody and other agent
US20220168416A1 (en) * 2013-08-01 2022-06-02 Five Prime Therapeutics, Inc. Afucosylated Anti-FGFR2IIIB Antibodies

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100196364A1 (en) * 2008-11-07 2010-08-05 Galaxy Biotech, Llc Monoclonal antibodies to fibroblast growth factor receptor 2
CN104066750A (zh) * 2011-11-23 2014-09-24 拜耳知识产权有限责任公司 抗fgfr2的抗体及其用途
CN104334724A (zh) * 2012-04-09 2015-02-04 第一三共株式会社 抗-fgfr2抗体
US20220168416A1 (en) * 2013-08-01 2022-06-02 Five Prime Therapeutics, Inc. Afucosylated Anti-FGFR2IIIB Antibodies
US20160317656A1 (en) * 2013-10-08 2016-11-03 Daiichi Sankyo Company, Limited Combination of anti-fgfr2 antibody and other agent

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