CN108640997A - 一种双特异性抗体 - Google Patents

一种双特异性抗体 Download PDF

Info

Publication number
CN108640997A
CN108640997A CN201810496026.8A CN201810496026A CN108640997A CN 108640997 A CN108640997 A CN 108640997A CN 201810496026 A CN201810496026 A CN 201810496026A CN 108640997 A CN108640997 A CN 108640997A
Authority
CN
China
Prior art keywords
antigen
binding site
chains
bispecific antibody
amino acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201810496026.8A
Other languages
English (en)
Inventor
蔡毓旻
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Priority to CN201810496026.8A priority Critical patent/CN108640997A/zh
Publication of CN108640997A publication Critical patent/CN108640997A/zh
Priority to CN201910219509.8A priority patent/CN109776684A/zh
Pending legal-status Critical Current

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
    • C07K16/241—Tumor Necrosis Factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/55—Glands not provided for in groups A61K35/22 - A61K35/545, e.g. thyroids, parathyroids or pineal glands
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/62—Leeches; Worms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/63—Arthropods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/21—Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232—Angelica
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/236—Ligusticum (licorice-root)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/238—Saposhnikovia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/284—Atractylodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/286—Carthamus (distaff thistle)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/288—Taraxacum (dandelion)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/34—Campanulaceae (Bellflower family)
    • A61K36/344—Codonopsis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/46—Eucommiaceae (Eucommia family), e.g. hardy rubber tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/481—Astragalus (milkvetch)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/486—Millettia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/56—Loganiaceae (Logania family), e.g. trumpetflower or pinkroot
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A61K36/714—Aconitum (monkshood)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A61K36/716—Clematis (leather flower)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/74—Rubiaceae (Madder family)
    • A61K36/748—Oldenlandia or Hedyotis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/756—Phellodendron, e.g. corktree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/80—Scrophulariaceae (Figwort family)
    • A61K36/804—Rehmannia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815—Lycium (desert-thorn)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/86—Violaceae (Violet family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
    • A61K36/8884—Arisaema, e.g. Jack in the pulpit
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/894—Dioscoreaceae (Yam family)
    • A61K36/8945—Dioscorea, e.g. yam, Chinese yam or water yam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A61K36/8994—Coix (Job's tears)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/90—Smilacaceae (Catbrier family), e.g. greenbrier or sarsaparilla
    • 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
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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]
    • 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]
    • 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
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Rheumatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Endocrinology (AREA)
  • Pain & Pain Management (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Virology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Cell Biology (AREA)
  • Insects & Arthropods (AREA)

Abstract

本发明提供一种双特异性抗体，具体地，所述双特异性抗体为抗TNF/IL23双特异性抗体，所述双特异性抗体为人源化lgG型抗体，所述双特异性抗体包括与肿瘤坏死因子TNF‑α特异性结合的第一抗原结合部位，还包括与白细胞介素IL‑23特异性结合的第二抗原结合部位，其中所述双特异抗体还包含通过一个或多个二硫键链间连接的第一Fc链及第二Fc链，该第一Fc链和第二Fc链通过共价键或连接体分别连接到第一抗原结合部位和第二抗原结合部位上。

Description

一种双特异性抗体
技术领域
本发明涉及抗体领域，尤其涉及一种双特异性抗体。
背景技术
单克隆抗体是只作用于单一抗原表位的高度特异性抗体，已被广泛用于许多疾病的治疗，例如，癌症、炎症和自身免疫性疾病、感染性疾病。但是，此类治疗分子如果单独使用，没有一种能够显示出足够的药效，这是由于疾病的复杂性，如癌症或炎症性疾病通常涉及多种疾病介导的分子通路以及信号通路之间的相叉作用。在这些情况下，靶向单一的分子不能提供最佳的治疗效果，而同时阻断多个靶点或者同一靶点的多个位点的分子能够改善治疗效果。同时，使用多特异性如双特异性分子的双靶向治疗可以简化新药开发过程，因为它是单一分子。和使用多个单特异分子的联合用药相比，对于患者和医疗工作者都是更方便的。
类风湿关节炎（RA）是一种病因未明的慢性、以炎性滑膜炎为主的系统性疾病。其特征是手、足小关节的多关节、对称性、侵袭性关节炎症，经常伴有关节外器官受累及血清类风湿因子阳性，可以导致关节畸形及功能丧失。RA的发病可能与遗传、感染、性激素等有关。RA关节炎的病理主要有滑膜衬里细胞增生、间质大量炎性细胞浸润，以及微血管的新生、血管翳的形成及软骨和骨组织的破坏等。
类风湿关节炎治疗的主要目的在于减轻关节炎症反应，抑制病变发展及不可逆骨质破坏，尽可能保护关节和肌肉的功能，最终达到病情完全缓解的目标。本发明提供一种双特异性抗体，对类风湿引起的腰腿关节疼痛、骨质增生、颈椎痛、坐骨神经痛、腿关节疼痛复水肿胀、肢体麻木的治疗效果显著。
发明内容
为了解决上述技术问题，本发明提供一种双特异性抗体。
本发明是以如下技术方案实现的：
一种双特异性抗体，所述双特异性抗体为抗TNF/IL23双特异性抗体，所述双特异性抗体为人源化lgG型抗体。
进一步地，所述双特异性抗体包括与肿瘤坏死因子TNF-α特异性结合的第一抗原结合部位，还包括与白细胞介素IL-23特异性结合的第二抗原结合部位，其中所述双特异抗体还包含通过一个或多个二硫键链间连接的第一Fc链及第二Fc链，该第一Fc链和第二Fc链通过共价键或连接体分别连接到第一抗原结合部位和第二抗原结合部位上。
进一步地，所述第一Fc链在如下位置包含2个氨基酸的替换，在第一Fc链上356位及379位氨基酸替换。
进一步地，所述第二Fc链在如下位置包含3个氨基酸的替换，第二Fc链上321位、407位及409位氨基酸替换。
进一步地，包含所述氨基酸替换的第一Fc链与第二Fc链更倾向于互相形成异源二聚体而不倾向于各自形成同源二聚体。
进一步地，所述第一抗原结合部位轻链可变区氨基酸序列如SEQ ID NO:1所示；所述第一抗原结合部位轻链恒定区氨基酸序列如SEQ ID NO:2所示。
进一步地，所述第一抗原结合部位重链可变区氨基酸序列如SEQ ID NO:3所示；所述第一抗原结合部位重链恒定区氨基酸序列如SEQ ID NO:4所示。
进一步地，所述第二抗原结合部位轻链可变区氨基酸序列如SEQ ID NO:5所示；所述第二抗原结合部位轻链恒定区氨基酸序列如SEQ ID NO:6所示。
进一步地，所述第二抗原结合部位重链可变区氨基酸序列如SEQ ID NO:7所示；所述第二抗原结合部位重链恒定区氨基酸序列如SEQ ID NO:8所示。
本发明的有益效果是：
单克隆抗体是只作用于单一抗原表位的高度特异性抗体，已被广泛用于许多疾病的治疗，例如，癌症、炎症和自身免疫性疾病、感染性疾病。但是，此类治疗分子如果单独使用，没有一种能够显示出足够的药效，这是由于疾病的复杂性，如癌症或炎症性疾病通常涉及多种疾病介导的分子通路以及信号通路之间的相叉作用。在这些情况下，靶向单一的分子不能提供最佳的治疗效果，而同时阻断多个靶点或者同一靶点的多个位点的分子能够改善治疗效果。同时，使用多特异性如双特异性分子的双靶向治疗可以简化新药开发过程，因为它是单一分子。和使用多个单特异分子的联合用药相比，对于患者和医疗工作者都是更方便的。
本发明还提供一种包含所述双特异性抗体的设备，所述设备提供的缓释层可以在用药后较长时间内持续释放药物，长效作用，血药浓度长时间恒定维持在有效浓度，减少“峰谷”现象；减少给药次数，对半衰期短或需频繁给药的药物，可以改善病人的顺应性；采用经皮给药可以不经过肝脏的“首过效应”和胃肠道的破坏，且皮肤间层还有储存作用，使药物浓度曲线平缓，避免了“峰谷现象”，提供可预定的和较长的作用时间，维持稳定持久的血药浓度，毒性和不良反应小，使用方便。
附图说明
图1是本实施例提供的一种双特异性抗体的示意图；
图2是本实施例提供的特种给药设备的示意图
图3是本实施例提供的特种给药设备的俯视图。
其中：1-设备本体，2-免疫药物层，3-中药药物层，4-缓释层，5-粘性区。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚，下面将对本发明作进一步地详细描述。下述实施例中所使用的试验方法如无特殊说明，均为常规方法；所使用的设备、原料、试剂等，如无特殊说明，均为可从常规商业途径购买得到的设备、原料、试剂。
实施例1：
一种特种给药设备，如图2所示，所述设备包括设备本体1，免疫药物层2，中药药物层3以及缓释层4，所述设备本体1为U型，外边缘凸出，外边缘设置有粘性区5，可以粘贴至人体任意位置，所述设备本体1由防水材料制成，所述免疫药物层与中药药物层之间设置有防水支撑层，如图3虚线所示，虚线内为免疫药物层2，虚线外为中药药物层3，所述设备本体1直径为4-10cm，具体可根据患处面积定制。
实施例2：
本发明缓释层的制备方法如下：将0.5% (w/v)中等分子量的壳聚糖溶液溶解于1% (w/v)乙酸中至终浓度为0.1%，获得第一分散液。向第一分散液中加入干粉质量相当于壳聚糖溶液中壳聚糖干粉质量的30%的3，4-二羟基肉桂酸，之后加入质量比为第一分散液0.01%的硬质胺后获得第二分散液，向所述第二分散液中加入固化剂，所述固化剂为甘羟铝，质量比为第二分散液的5.7%，加入固化基材，所述固化基材为不完全中和型NP-700聚丙烯酸钠，质量比为第二分散液的26%，加入固化调节剂，所述固化调节剂为酒石酸，质量比为第二分散液的12.1%，加入增稠剂和络合剂，所述增粘剂为60%聚乙烯吡咯烷酮PVPK90和40%羟甲基纤维素钠CMC-Na组成的混合物，所述混合物质量比为第二分散液的5.8%，络合剂为乙二胺四乙酸二钠，质量比为第二分散液的2.2%。上述过程于65℃下进行，将所有成分搅拌均匀后倒入模具，冷却后制成缓释层，所述缓释层呈凝胶状，厚度为2mm，能够紧密贴合人体皮肤，具有生物大分子穿透能力，但同时能起到一定生物大分子滞留效果，使得缓释层具有较强的药物穿透效果和缓释效果，3，4-二羟基肉桂酸具有较强的皮肤渗透能力，能够穿透角质层运送有效量的药液至皮下，使药液在皮下弥散分布，有效作用时间长，药物吸收率更高。
经皮给药可以不经过肝脏的“首过效应”和胃肠道的破坏，且皮肤间层还有储存作用，使药物浓度曲线平缓，避免了“峰谷现象”，提供可预定的和较长的作用时间，维持稳定持久的血药浓度，毒性和不良反应小，使用方便。
实施例3：
本发明参考WO2013060867中描述的一种大规模生产异二聚体双特异抗体的方法，该方法先还原两种混合的同源二聚体形式抗体，然后通过在这两种同源二聚体抗体的Fc区引入不对称氨基酸突变从而促使不同抗体的Fab臂发生交换，最后通过氧化铰链区的链间二硫键形成稳定的双特异抗体。
本发明所述免疫药物层中放置有抗TNF/IL23双特异性抗体，所述双特异性抗体为人源化lgG型抗体，所述双特异性抗体包括与肿瘤坏死因子TNF-α特异性结合的第一抗原结合部位，还包括与白细胞介素IL-23特异性结合的第二抗原结合部位，其中所述双特异抗体包含通过一个或多个二硫键链间连接的第一Fc链及第二Fc链，该第一Fc链和第二Fc链通过共价键或连接体分别连接到第一抗原结合部位和第二抗原结合部位上，并且第一Fc链和第二Fc链在如下位置包含5个氨基酸的替换：
重链恒定区为人IgG1，在第一Fc链上356位及379位氨基酸替换，第二Fc链上321位、407位及409位氨基酸的替换，包含上述氨基酸替换的第一Fc链与第二Fc链更倾向于互相形成异源二聚体而不倾向于各自形成同源二聚体，具体地，第一Fc链T356L 及D379Q替换，第二Fc链L321E、Y407K 及I409V替换。
进一步地，所述第一抗原结合部位轻链可变区氨基酸序列如SEQ ID NO:1所示；轻链恒定区氨基酸序列如SEQ ID NO:2所示；重链可变区氨基酸序列如SEQ ID NO:3所示；重链恒定区氨基酸序列如SEQ ID NO:4所示。所述第二抗原结合部位轻链可变区氨基酸序列如SEQ ID NO:5所示；轻链恒定区氨基酸序列如SEQ ID NO:6所示；重链可变区氨基酸序列如SEQ ID NO:7所示；重链恒定区氨基酸序列如SEQ ID NO:8所示。通过PCR的方法分别扩增轻链可变区以及轻链恒定区，重链可变区以及重链恒定区。本申请中所有PCR反应均使用NEB公司的Phusion超保真DNA聚合酶（F-530L）。PCR引物根据碱基互补原则以及酶切位点的需要进行常规设计，双特异性抗体参考常规方法合成，上述抗体注射入免疫药物层中。
实施例4：
本发明所述中药药物层中放置有中药配伍如下：
黄芪30份，党参15份，白术8份，当归15份，白芍6份，杜仲6份，桑寄生6份，川牛膝10份，独活9份，防风7.5份，鸡血藤15份，千年健10份，金刚刺10份，枸杞子32份，土茯苓25份，萆蘇19份，蒲公英12份，紫花地丁25份，白花蛇舌草25份，黄柏5份，生地黄8份，丹参20份，薏苡仁30份，桃仁15份，红花10份，熟地黄10份，川芎15份，赤芍6份，制南星6份，白芥子6份，制僵蚕10份，地龙10份，露蜂房10份，威灵仙19份，路路通15份，生马钱子23份，生草乌15份，生南星25份，冰片2份，林麝麝香一份。
将黄芪，党参，白术，当归，白芍，杜仲，桑寄生，川牛膝，独活，防风，鸡血藤，千年健，金刚刺，枸杞子，土茯苓，萆蘇，蒲公英，紫花地丁切碎，剩余成分研磨至80目，将香油放入锅内加热，将黄芪，党参，白术，当归，白芍，杜仲，桑寄生，川牛膝，独活，防风，鸡血藤，千年健，金刚刺，枸杞子，土茯苓，萆蘇，蒲公英，紫花地丁同时入锅，文火煎炸，药料炸至黄褐色时，取出药料，去渣滤净得药油；将药油放入干净的铜锅内，加热至120℃左右，将剩余成分加入锅中搅拌，水气散尽，松散为度，急住火，沉淀后取上清液，注射入中药药物层。
实施例5：
辅助治疗类风湿性关节炎的设备的治疗效果
(1) 风湿引起的腰腿关节疼痛
诊断标准：由风湿引起的腰腿关节疼痛，主要症状为腰腿关节局部有明显的红、肿、热、痛及触痛，疼痛无定处，呈游走性。
痊愈的标准为：风湿引起的腰腿关节疼痛的主要表现症状完全消失。
有效的标准为：风湿引起的腰腿关节疼痛的主要表现症状减轻。
无效的标准为：风湿引起的腰腿关节疼痛的主要表现症状没有改变。
(2) 骨质增生
诊断标准：通过骨科检查，患者的骨关节边缘上增生骨质，疼痛难忍。
痊愈的标准为：患者的骨关节边缘上增生骨质完全消失，无疼痛。
有效的标准为：患者的骨关节边缘上增生骨质减小，疼痛减轻。
无效的标准为：患者的骨关节边缘上增生骨质没有改变，疼痛无好转。
(3) 颈椎痛
诊断标准：颈椎痛主要症状为颈椎酸痛，肩膀疼痛或发硬、头晕、耳鸣、四肢发麻。
痊愈的标准为：颈椎痛主要表现症状完全消失。
有效的标准为：颈椎痛主要表现症状减轻。
无效的标准为：颈椎痛主要表现症状没有改变。
(4) 坐骨神经痛
诊断标准：由腰椎间盘脱出症引起的坐骨神经痛，主要症状为坐骨神经通路及其分布区内疼痛，自臀部沿大腿后侧、小腿外侧向远端放射。
痊愈的标准为：坐骨神经痛主要表现症状完全消失。
有效的标准为：坐骨神经痛主要表现症状减轻。
无效的标准为：坐骨神经痛主要表现症状没有改变。
(5) 腿关节复水肿胀
诊断标准：由风湿、类风湿引起的腿关节复水肿胀，主要症状为腿关节疼痛复水肿胀。
痊愈的标准为：腿关节疼痛复水肿胀症状完全消失。
有效的标准为：腿关节疼痛复水肿胀症状减轻。
无效的标准为：腿关节疼痛复水肿胀症状没有改变。
(6) 肢体麻木
诊断标准：由风湿、类风湿引起的肢体麻木，主要症状为肢体麻木。
痊愈的标准为：肢体麻木症状完全消失。
有效的标准为：肢体麻木症状减轻。
无效的标准为：肢体麻木症状没有改变。
经过998例患者的临床使用，其中472例患者为风湿引起的腰腿关节疼痛，115例为骨质增生，98例为颈椎痛，有101例坐骨神经痛，116例为腿关节疼痛复水肿胀，96例为肢体麻木。年龄最大的84岁，年龄最小的为23岁，男性患者347名，女性为651名，每贴48小时更换一次，30日为一疗程。850例贴2个疗程后有效；有578例贴13个疗程后周期后痊愈；其余未痊愈，但是症状有减轻趋势；总治愈率为57.9％。
以上所揭露的仅为本发明较佳实施例而已，当然不能以此来限定本发明之权利范围，因此依本发明权利要求所作的等同变化，仍属本发明所涵盖的范围。

Claims (9)

1.一种双特异性抗体，其特征在于，所述双特异性抗体为抗TNF/IL23双特异性抗体，所述双特异性抗体为人源化lgG型抗体。
2.根据权利要求1所述双特异性抗体，其特征在于，所述双特异性抗体包括与肿瘤坏死因子TNF-α特异性结合的第一抗原结合部位，还包括与白细胞介素IL-23特异性结合的第二抗原结合部位，其中所述双特异抗体还包含通过一个或多个二硫键链间连接的第一Fc链及第二Fc链，该第一Fc链和第二Fc链通过共价键或连接体分别连接到第一抗原结合部位和第二抗原结合部位上。
3.根据权利要求1-2任一所述的双特异性抗体，其特征在于，所述第一Fc链在如下位置包含2个氨基酸的替换，在第一Fc链上356位及379位氨基酸替换。
4.根据权利要求1-3任一所述的双特异性抗体，其特征在于，所述第二Fc链在如下位置包含3个氨基酸的替换，第二Fc链上321位、407位及409位氨基酸替换。
5.根据权利要求1-4所述的双特异性抗体，其特征在于，包含所述氨基酸替换的第一Fc链与第二Fc链更倾向于互相形成异源二聚体而不倾向于各自形成同源二聚体。
6.根据权利要求5所述双特异性抗体，其特征在于，所述第一抗原结合部位轻链可变区氨基酸序列如SEQ ID NO:1所示；所述第一抗原结合部位轻链恒定区氨基酸序列如SEQ IDNO:2所示。
7.根据权利要求6所述双特异性抗体，其特征在于，所述第一抗原结合部位重链可变区氨基酸序列如SEQ ID NO:3所示；所述第一抗原结合部位重链恒定区氨基酸序列如SEQ IDNO:4所示。
8.根据权利要求7所述双特异性抗体，其特征在于，所述第二抗原结合部位轻链可变区氨基酸序列如SEQ ID NO:5所示；所述第二抗原结合部位轻链恒定区氨基酸序列如SEQ IDNO:6所示。
9.根据权利要求8所述双特异性抗体，其特征在于，所述第二抗原结合部位重链可变区氨基酸序列如SEQ ID NO:7所示；所述第二抗原结合部位重链恒定区氨基酸序列如SEQ IDNO:8所示。
CN201810496026.8A 2018-05-22 2018-05-22 一种双特异性抗体 Pending CN108640997A (zh)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN201810496026.8A CN108640997A (zh) 2018-05-22 2018-05-22 一种双特异性抗体
CN201910219509.8A CN109776684A (zh) 2018-05-22 2019-03-21 一种双特异性抗体

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810496026.8A CN108640997A (zh) 2018-05-22 2018-05-22 一种双特异性抗体

Publications (1)

Publication Number Publication Date
CN108640997A true CN108640997A (zh) 2018-10-12

Family

ID=63757468

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201810496026.8A Pending CN108640997A (zh) 2018-05-22 2018-05-22 一种双特异性抗体
CN201910219509.8A Pending CN109776684A (zh) 2018-05-22 2019-03-21 一种双特异性抗体

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN201910219509.8A Pending CN109776684A (zh) 2018-05-22 2019-03-21 一种双特异性抗体

Country Status (1)

Country Link
CN (2) CN108640997A (zh)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111100211A (zh) * 2019-01-30 2020-05-05 武汉九州钰民医药科技有限公司 一种Fc融合蛋白及其应用
CN111100210A (zh) * 2019-01-30 2020-05-05 武汉九州钰民医药科技有限公司 一种Fc融合蛋白及其应用
WO2020135555A1 (zh) * 2018-12-28 2020-07-02 长春金赛药业股份有限公司 二价双特异性抗体及其制备方法、编码基因、宿主细胞、组合物
WO2024175031A1 (zh) * 2023-02-21 2024-08-29 江苏恒瑞医药股份有限公司 Il-36r结合蛋白及其医药用途

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101668531A (zh) * 2007-02-28 2010-03-10 先灵公司 用于治疗免疫病症的联合治疗
CN104114579A (zh) * 2011-10-27 2014-10-22 根马布股份公司 异二聚体蛋白的生成
WO2016073406A1 (en) * 2014-11-05 2016-05-12 Eli Lilly And Company Anti-tnf-/anti-il-23 bispecific antibodies

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2749383T3 (es) * 2014-11-06 2020-03-20 Hoffmann La Roche Variantes de la región Fc con unión al FcRn modificada y procedimientos de uso
CN106883297B (zh) * 2015-12-16 2019-12-13 苏州康宁杰瑞生物科技有限公司 基于ch3结构域的异二聚体分子、其制备方法及用途

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101668531A (zh) * 2007-02-28 2010-03-10 先灵公司 用于治疗免疫病症的联合治疗
CN104114579A (zh) * 2011-10-27 2014-10-22 根马布股份公司 异二聚体蛋白的生成
WO2016073406A1 (en) * 2014-11-05 2016-05-12 Eli Lilly And Company Anti-tnf-/anti-il-23 bispecific antibodies

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
朱建华 等: "α通过血清中TNF-α、IL-17、IL-23的水平研究慢性牙周炎和类风湿性关节炎的相关性", 《口腔医学研究》 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020135555A1 (zh) * 2018-12-28 2020-07-02 长春金赛药业股份有限公司 二价双特异性抗体及其制备方法、编码基因、宿主细胞、组合物
CN111100211A (zh) * 2019-01-30 2020-05-05 武汉九州钰民医药科技有限公司 一种Fc融合蛋白及其应用
CN111100210A (zh) * 2019-01-30 2020-05-05 武汉九州钰民医药科技有限公司 一种Fc融合蛋白及其应用
CN111100210B (zh) * 2019-01-30 2022-04-19 武汉九州钰民医药科技有限公司 一种Fc融合蛋白及其应用
WO2024175031A1 (zh) * 2023-02-21 2024-08-29 江苏恒瑞医药股份有限公司 Il-36r结合蛋白及其医药用途

Also Published As

Publication number Publication date
CN109776684A (zh) 2019-05-21

Similar Documents

Publication Publication Date Title
CN108640997A (zh) 一种双特异性抗体
CN108578497A (zh) 一种用于治疗人体疼痛的外用热敷磁灸泥及其制作方法
CN104127618A (zh) 一种治疗骨弊的膏药
CN116392563B (zh) 一种治疗乳腺结节的中药组合物及其制剂和应用
CN103736067A (zh) 一种治疗腰椎间盘突症的中药组合物
CN104491819A (zh) 一种治疗骨折、肌腱损伤的中药膏药及其制备方法
CN108514598A (zh) 一种预防和/或治疗类风湿关节炎的组合物及制备与应用
CN104491740A (zh) 一种治疗肝癌的中药组合物及其制备方法
CN103893653A (zh) 治疗腰间盘突出的中药
CN1290550C (zh) 一种治疗风湿、类风湿、骨质增生及骨折的中药组合物及其制备方法
CN108420978A (zh) 一种治疗关节炎中药
CN110934979A (zh) 一种治疗颈椎病的黑膏药及其制备方法
CN1843421A (zh) 一种治疗风湿疾病的药物
CN108404285A (zh) 一种辅助治疗类风湿性关节炎的设备
CN102579710B (zh) 一种治疗强直性脊柱炎的中药及其制备方法
CN103705864B (zh) 一种治疗颈椎、腰椎病的蒸骨热敷膏
CN1313120C (zh) 筋骨片在制备治疗肩周炎的药物中的应用
CN102406792B (zh) 一种快速促进骨折愈合的药物组合物
CN101590208B (zh) 一种治疗类风湿关节炎的药物组合物及其制备方法
CN106511630B (zh) 一种治疗风湿性关节炎的外用药物及其制备方法
CN104958586A (zh) 一种用于治疗腰疼的中药制剂
CN1321678C (zh) 一种治疗甲肝病和乙肝病的丸剂及其制备方法
CN100418573C (zh) 一种治疗强直性脊柱炎的外用中药
CN102552823A (zh) 一种治疗骨性关节炎的药物及其制备方法
CN101361955B (zh) 一种治疗类风湿疾病的中药组合物

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20181012

WD01 Invention patent application deemed withdrawn after publication