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AR133647A1 - ANTI-IL-13 MULTISPECIFIC ANTIBODY CONSTRUCTS AND THEIR USES - Google Patents

ANTI-IL-13 MULTISPECIFIC ANTIBODY CONSTRUCTS AND THEIR USES

Info

Publication number
AR133647A1
AR133647A1 ARP240102257A ARP240102257A AR133647A1 AR 133647 A1 AR133647 A1 AR 133647A1 AR P240102257 A ARP240102257 A AR P240102257A AR P240102257 A ARP240102257 A AR P240102257A AR 133647 A1 AR133647 A1 AR 133647A1
Authority
AR
Argentina
Prior art keywords
amino acid
antibody
construct
cdr
seq
Prior art date
Application number
ARP240102257A
Other languages
Spanish (es)
Inventor
Yan Zheng
Jie Tang
Yan Wang
Rui Zhang
Minghui Xu
Wenyan Shen
Danming Tang
Original Assignee
Proteologix Us Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Proteologix Us Inc filed Critical Proteologix Us Inc
Publication of AR133647A1 publication Critical patent/AR133647A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/244—Interleukins [IL]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/35—Valency
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/522—CH1 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/53—Hinge
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pain & Pain Management (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

La presente invención se refiere a constructos multiespecíficos que se unen específicamente a IL-13 y un segundo antígeno diana (por ejemplo, TSLP, IL-17A, IL-17F, TNF-a, e IFN-g). Además se proporcionan constructos de anticuerpos que se unen específicamente a IL-13. Además se proporcionan composiciones, kits, métodos de uso (por ejemplo, para tratar una enfermedad inflamatoria), y métodos de elaboración de las mismas. Reivindicación 1: Un constructo multiespecífico que comprende: (1) un primer resto de anticuerpo que se une específicamente a interleucina-13 (IL-13), y (2) un segundo resto de anticuerpo que se une específicamente a un segundo antígeno. Reivindicación 39: Un constructo de anticuerpo aislado (constructo de anticuerpo anti-IL-13) que comprende un resto de anticuerpo que se une específicamente a interleucina-13 (IL-13) (resto de anticuerpo anti-IL-13), en donde el resto de anticuerpo anti-IL-13 comprende una región variable de cadena pesada (VH) y una región variable de cadena ligera (VL), y en donde: la VH comprende (i) una CDR-H1 que comprende una secuencia de aminoácidos de la SEQ ID Nº 66, o una variante de la misma que comprende hasta 3 variaciones de aminoácidos; (ii) una CDR-H2 que comprende una secuencia de aminoácidos de la SEQ ID Nº 67, o una variante de la misma que comprende hasta 3 variaciones de aminoácidos; y (iii) una CDR-H3 que comprende una secuencia de aminoácidos de la SEQ ID Nº 68, o una variante de la misma que comprende hasta 3 variaciones de aminoácidos; y la VL comprende (i) una CDR-L1 que comprende una secuencia de aminoácidos de la SEQ ID Nº 70, o una variante de la misma que comprende hasta 3 variaciones de aminoácidos; (ii) una CDR-L2 que comprende una secuencia de aminoácidos de la SEQ ID Nº 71, o una variante de la misma que comprende hasta 3 variaciones de aminoácidos; y (iii) una CDR-L3 que comprende una secuencia de aminoácidos de la SEQ ID Nº 72, o una variante de la misma que comprende hasta 3 variaciones de aminoácidos. Reivindicación 52: Una composición farmacéutica que comprende (i) el constructo multiespecífico de cualquiera de las reivindicaciones 1 - 38, o el constructo de anticuerpo anti-IL-13 aislado de cualquiera de las reivindicaciones 39 - 51; y (ii) un portador farmacéuticamente aceptable. Reivindicación 53: Un ácido nucleico aislado o un vector que codifica uno o más polipéptidos del constructo multiespecífico de cualquiera de las reivindicaciones 1 - 38 o el constructo de anticuerpo anti-IL-13 aislado de cualquiera de las reivindicaciones 39 - 51. Reivindicación 54: Una célula huésped que comprende el ácido nucleico aislado o el vector de la reivindicación 53. Reivindicación 55: Un método para tratar una enfermedad inflamatoria en un individuo, que comprende administrar al individuo una cantidad efectiva de la composición farmacéutica de la reivindicación 52. Reivindicación 57: Un método para producir un constructo multiespecífico o un constructo de anticuerpo anti-IL-13, que comprende i) cultivar una célula huésped que comprende el ácido nucleico aislado o el vector de la reivindicación 53, o la célula huésped de la reivindicación 54, bajo una condición adecuada para la expresión del constructo multiespecífico o el constructo de anticuerpo anti-IL-13; y ii) obtener el constructo multiespecífico expresado o constructo de anticuerpo anti-IL-13.The present invention relates to multispecific constructs that bind specifically to IL-13 and a second target antigen (e.g., TSLP, IL-17A, IL-17F, TNF-α, and IFN-γ). Antibody constructs that bind specifically to IL-13 are also provided. Furthermore, compositions, kits, methods of use (e.g., for treating an inflammatory disease), and methods of preparation thereof are provided. Claim 1: A multispecific construct comprising: (1) a first antibody residue that binds specifically to interleukin-13 (IL-13), and (2) a second antibody residue that binds specifically to a second antigen. Claim 39: An isolated antibody construct (anti-IL-13 antibody construct) comprising an antibody residue specifically binding to interleukin-13 (IL-13) (anti-IL-13 antibody residue), wherein the anti-IL-13 antibody residue comprises a heavy chain variable region (HV) and a light chain variable region (LV), and wherein: the HV comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID No. 66, or a variant thereof comprising up to 3 amino acid variations; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID No. 67, or a variant thereof comprising up to 3 amino acid variations; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID No. 68, or a variant thereof comprising up to 3 amino acid variations; and the VL comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID No. 70, or a variant thereof comprising up to 3 amino acid variations; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID No. 71, or a variant thereof comprising up to 3 amino acid variations; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID No. 72, or a variant thereof comprising up to 3 amino acid variations. Claim 52: A pharmaceutical composition comprising (i) the multispecific construct of any of claims 1-38, or the anti-IL-13 antibody construct isolated from any of claims 39-51; and (ii) a pharmaceutically acceptable carrier. Claim 53: An isolated nucleic acid or a vector encoding one or more polypeptides of the multispecific construct of any of claims 1-38 or the anti-IL-13 antibody construct isolated from any of claims 39-51. Claim 54: A host cell comprising the isolated nucleic acid or the vector of claim 53. Claim 55: A method for treating an inflammatory disease in an individual, comprising administering to the individual an effective amount of the pharmaceutical composition of claim 52. Claim 57: A method for producing a multispecific construct or an anti-IL-13 antibody construct, comprising (i) culturing a host cell comprising the isolated nucleic acid or the vector of claim 53, or the host cell of claim 54, under a condition suitable for the expression of the multispecific construct or the anti-IL-13 antibody construct; and ii) obtain the expressed multispecific construct or anti-IL-13 antibody construct.

ARP240102257A 2023-08-25 2024-08-23 ANTI-IL-13 MULTISPECIFIC ANTIBODY CONSTRUCTS AND THEIR USES AR133647A1 (en)

Applications Claiming Priority (1)

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US202363578946P 2023-08-25 2023-08-25

Publications (1)

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ID=92800531

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AR (1) AR133647A1 (en)
TW (1) TW202525846A (en)
WO (1) WO2025049345A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN120795162A (en) * 2024-04-02 2025-10-17 康诺亚生物医药科技（成都）有限公司 Bispecific antibodies against IL-13 and TSLP and uses thereof

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