NZ761547B2 - Bispecific antibody - Google Patents
Bispecific antibody Download PDFInfo
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- NZ761547B2 NZ761547B2 NZ761547A NZ76154719A NZ761547B2 NZ 761547 B2 NZ761547 B2 NZ 761547B2 NZ 761547 A NZ761547 A NZ 761547A NZ 76154719 A NZ76154719 A NZ 76154719A NZ 761547 B2 NZ761547 B2 NZ 761547B2
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Classifications
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
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- C07—ORGANIC CHEMISTRY
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- 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
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- 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]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
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- C07—ORGANIC CHEMISTRY
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- 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
Abstract
The present invention addresses the problem of providing a novel drug for the prevention of autoimmune diseases, the suppression of the progression of the symptoms of autoimmune diseases, the suppression of the recurrence of autoimmune diseases, or the treatment of autoimmune diseases. As a result of diligent investigation, the inventors of the present invention have focused on PD-1/CD3 bispecific antibodies as substances that can solve the abovementioned problem and have confirmed that said bispecific antibodies make it possible to achieve pharmaceuticals that reduce the occurrence of the adverse effects known as infusion-related reaction and cytokine release syndrome. In addition, the inventors have confirmed that said bispecific antibodies allow for interaction between PD-1 and its ligand PD-L1 and have discovered that said feature contributes to enhanced and sustained activity.
Claims (36)
1. A PD-1/CD3 bispecific antibody or antibody fragment thereof, comprising the first arm specifically binding to PD-1 and the second arm specifically binding to CD3, wherein the first arm specifically binding to PD-1 comprises any one of VH selected from: (A) a VH having (a) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 18; (b) a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 19; and (c) a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 20; (B) a VH having (a) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 6; (b) a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 7; and (c) a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 8; (C) a VH having (a) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 9; (b) a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 10; and (c) a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 11; (D) a VH having (a) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 12; (b) a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 13, and (c) a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 14; and (E) a VH having (a) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 15; (b) a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 16; and (c) a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 17; and (F) a VL having (a) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 26; (b) a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 27; and (c) a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 28; and wherein the second arm specifically binding to CD3 comprises: (A) a VH having (a) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 37; (b) a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 38; and (c) a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 39, and (B) a VL having (a) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 26; (b) a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 27; and (c) a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 28.
2. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 1, wherein (i) the VH of the first arm specifically binding to PD-1 has: (a) the VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 18, (b) the VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 19, and (c) the VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 20; and (ii) the VH of the second arm specifically binding to CD3 has: (a) the VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 37, (b) the VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 38, and (c) the VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 39.
3. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 1, wherein (i) the VH of the first arm specifically binding to PD-1 has: (a) the VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 6, (b) the VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 7, and (c) the VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 8; and (ii) the VH of the second arm specifically binding to CD3 has: (a) the VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 37, (b) the VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 38, and (c) the VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 39.
4. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 1, wherein (i) the VH of the first arm specifically binding to PD-1 has: (a) the VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 9, (b) the VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 10, and (c) the VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 11; and (ii) the VH of the second arm specifically binding to CD3 has: (a) the VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 37, (b) the VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 38, and (c) the VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 39.
5. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 1, wherein (i) the VH of the first arm specifically binding to PD-1 has (a) the VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 12, (b) the VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 13, and (c) the VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 14, and (ii) the VH of the second arm specifically binding to CD3 has: (a) the VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 37, (b) the VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 38, and (c) the VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 39.
6. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 1, wherein (i) the VH of the first arm specifically binding to PD-1 has: (a) the VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 15, (b) the VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 16, and (c) the VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 17; and (ii) the VH of the second arm specifically binding to CD3 has: (a) the VH-CDR1 comprising the amino acid sequence set forth in SEQ ID No. 37, (b) the VH-CDR2 comprising the amino acid sequence set forth in SEQ ID No. 38, and (c) the VH-CDR3 comprising the amino acid sequence set forth in SEQ ID No. 39.
7. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to any one of claims 1 to 6, wherein the VH of the first arm specifically binding to PD-1 comprises the amino acid sequence set forth in any one selected from SEQ ID No. 5, SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, and SEQ ID No. 4, or an amino acid sequence having at least 80% identity to VH amino acid sequence thereof.
8. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to any one of claims 1 to 7, wherein the VH of the second arm specifically binding to CD3 comprises the amino acid sequence set forth in SEQ ID No. 36, or an amino acid sequence having an identity of at least 80% to VH amino acid sequence thereof.
9. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 1, wherein the VH of the first arm specifically binding to PD-1 comprises the amino acid sequence set forth in any one selected from SEQ ID No. 5, SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, and SEQ ID No. 4; and the VH of the second arm specifically binding to CD3 comprises the amino acid sequence set forth in SEQ ID No. 36.
10. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 1 or 2, wherein the VH of the first arm specifically binding to PD-1 comprises the amino acid sequence set forth in SEQ ID No. 5; and the VH of the second arm specifically binding to CD3 comprises the amino acid sequence set forth in SEQ ID No. 36.
11. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 1 or 3, wherein the VH of the first arm specifically binding to PD-1 comprises the amino acid sequence set forth in SEQ ID No. 1; and the VH of the second arm specifically binding to CD3 comprises the amino acid sequence set forth in SEQ ID No. 36.
12. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 1 or 4, wherein the VH of the first arm specifically binding to PD-1 comprises the amino acid sequence set forth in SEQ ID No. 2; and the VH of the second arm specifically binding to CD3 comprises the amino acid sequence set forth in SEQ ID No. 36.
13. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 1 or 5, wherein the VH of the first arm specifically binding to PD-1 comprises the amino acid sequence set forth in SEQ ID No. 3; and the VH of the second arm specifically binding to CD3 comprises the amino acid sequence set forth in SEQ ID No. 36.
14. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 1 or 6, wherein the VH of the first arm specifically binding to PD-1 comprises the amino acid sequence set forth in SEQ ID No. 4; and the VH of the second arm specifically binding to CD3 comprises the amino acid sequence set forth in SEQ ID No. 36.
15. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to any one of claims 1 to 14, wherein the first arm specifically binding to PD-1 and/or the second arm specifically binding to CD3 have the VL comprising the amino acid sequence set forth in SEQ ID No. 25.
16. A PD-1/CD3 bispecific antibody or antibody fragment thereof, having the first arm specifically binding to PD-1 and the second arm specifically binding to CD3, wherein (A) the first arm specifically binding to PD-1 has the VH comprising the amino acid sequence set forth in any one selected from SEQ ID No. 5, SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, and SEQ ID No. 4, and the VL comprising the amino acid sequence set forth in SEQ ID No. 25; and (B) the second arm specifically binding to CD3 has the VH comprising the amino acid sequence set forth in SEQ ID No. 36; and the VL comprising the amino acid sequence set forth in SEQ ID No. 25.
17. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to any one of claims 1 to 16, wherein the PD-1/CD3 bispecific antibody is an IgG antibody.
18. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 17, which is an IgG antibody or an IgG antibody.
19. The PD-1/CD3 bispecific antibody or an antibody fragment thereof according to claim 17, which is an IgG antibody.
20. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 19, wherein the binding to an Fc receptor is eliminated or reduced.
21. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 20, wherein in two heavy chain constant regions of the PD-1/CD3 bispecific IgG antibody, leucine at position 235 according to the EU numbering system is substituted with glycine, and/or glycine at position 236 according to the EU numbering system is substituted with arginine.
22. The PD-1/CD3 bispecific antibody or an antibody fragment thereof according to any one of claims 19 to 21, wherein in a constant region of a heavy chain having a VH of the first arm specifically binding to PD-1, leucine at position 351 according to the EU numbering system is substituted with lysine and threonine at position 366 according to the EU numbering system is substituted with lysine; and in a constant region of a heavy chain having a VH of the second arm specifically binding to CD3, leucine at position 351 according to the EU numbering system is substituted with aspartic acid and leucine at position 368 according to the EU numbering system is substituted with glutamic acid.
23. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to any one of claims 19 to 21, wherein in a constant region of a heavy chain having a VH of the first arm specifically binding to PD-1, leucine at position 351 according to the EU numbering system is substituted with aspartic acid, and leucine at position 368 is substituted with glutamic acid, and in a constant region of a heavy chain having a VH of the second arm specifically binding to CD3, leucine at position 351 according to the EU numbering system is substituted with lysine, and threonine at position 366 according to the EU numbering system is substituted with lysine.
24. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to any one of claims 19 to 23, wherein in two heavy chain constant regions of the PD-1/CD3 bispecific antibody, lysine at position 447 according to the EU numbering system is deleted.
25. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 18, wherein the PD-1/CD3 bispecific antibody is an IgG antibody, and in two heavy chain constant regions, serine at position 228 according to the EU numbering system is substituted with proline, respectively.
26. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to any one of claims 1 to 20, wherein the heavy chain having the VH of the first arm specifically binding to PD-1 has a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID No. 23.
27. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to any one of claims 1 to 20 or 26, wherein the heavy chain having the VH of the second arm specifically binding to CD3 has a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID No. 24.
28. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to any one of claims 1 to 27, wherein the light chain having the VL of the first arm specifically binding to PD-1 and/or the light chain having VL of the second arm specifically binding to CD3 have a light chain constant region comprising the amino acid sequence set forth in SEQ ID No. 29.
29. A PD-1/CD3 bispecific antibody or antibody fragment thereof, having the first arm specifically binding to PD-1 and the second arm specifically binding to CD3, wherein: (A) a heavy chain having the VH of the first arm specifically binding to PD-1 has the VH comprising the amino acid sequence set forth in any one selected from SEQ ID No. 5, SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, and SEQ ID No. 4, and the heavy chain constant region comprising the amino acid sequence set forth in SEQ ID No. 23; (B) a light chain having the VL of the first arm specifically binding to PD-1 has the VL comprising the amino acid sequence set forth in SEQ ID No. 25, and the light chain constant region comprising the amino acid sequence set forth in SEQ ID No. 29; (C) a heavy chain having the VH of the second arm specifically binding to CD3, has the VH comprising the amino acid sequence set forth in SEQ ID No. 36, and the heavy chain constant region comprising the amino acid sequence set forth in SEQ ID No. 24; and (D) a light chain having the VL of the second arm specifically binding to CD3 has the VL comprising the amino acid sequence set forth in SEQ ID No. 25, and the light chain constant region comprising the amino acid sequence set forth in SEQ ID No. 29.
30. A PD-1/CD3 bispecific antibody having the first arm specifically binding to PD-1 and the second arm specifically binding to CD3, wherein: (A) a heavy chain having the VH of the first arm specifically binding to PD-1 has the VH comprising the amino acid sequence set forth in SEQ ID No. 5, and the heavy chain constant region comprising the amino acid sequence set forth in SEQ ID No. 23; (B) a light chain having the VL of the first arm specifically binding to PD-1 has the VL comprising the amino acid sequence set forth in SEQ ID No. 25, and the light chain constant region comprising the amino acid sequence set forth in SEQ ID No. 29; (C) a heavy chain having the VH of the second arm specifically binding to CD3, has the VH comprising the amino acid sequence set forth in SEQ ID No. 36, and the heavy chain constant region comprising the amino acid sequence set forth in SEQ ID No. 24; and (D) a light chain having the VL of the second arm specifically binding to CD3 has the VL comprising the amino acid sequence set forth in SEQ ID No. 25, and the light chain constant region comprising the amino acid sequence set forth in SEQ ID No. 29.
31. A pharmaceutical composition comprising the PD-1/CD3 bispecific antibody or antibody fragment thereof selected from any one of claims 1 to 30, and a pharmaceutically acceptable carrier.
32. Use of the PD-1/CD3 bispecific antibody or antibody fragment thereof according to any one of claims 1 to 30 in the manufacture of a medicament for preventing, suppressing symptom progression or recurrence of, and/or treating autoimmune diseases.
33. The use according to claim 32, wherein the autoimmune diseases include Behcet's disease, systemic lupus erythematosus, chronic discoid lupus erythematosus, multiple sclerosis, scleroderma, polymyositis, dermatomyositis, periarteritis nodosa, aortitis syndrome, malignant rheumatoid arthritis, rheumatoid arthritis, juvenile idiopathic arthritis, spondyloarthritis, mixed connective tissue disease, Sjogren's syndrome, adult Still's disease, vasculitis, allergic granulomatous vasculitis, hypersensitivity vasculitis, rheumatoid vasculitis, large vessel vasculitis, ANCA associated vasculitis, Cogan's syndrome, RS3PE, temporal arteritis, polymyalgia rheumatica, fibromyalgia, antiphospholipid antibody syndrome, eosinophilic fasciitis, IgG4-related disease, Guillain-Barre syndrome, myasthenia gravis, chronic atrophic gastritis, autoimmune hepatitis, non-alcoholic steatohepatitis, primary biliary cirrhosis, Goodpasture's syndrome, rapidly progressive glomerulonephritis, megaloblastic anemia, autoimmune hemolytic anemia, pernicious anemia, autoimmune neutropenia, idiopathic thrombocytopenic purpura, Basedow disease, Hashimoto disease, autoimmune adrenal insufficiency, primary hypothyroidism, Addison's disease, idiopathic Addison's disease, type I diabetes mellitus, slowly progressive type I diabetes mellitus, focal scleroderma, psoriasis, psoriatic arthritis, bullous pemphigoid, pemphigus, pemphigoid, gestational herpes, linear IgA bullous dermatosis, acquired epidermolysis bullosa, alopecia areata, vitiligo, vitiligo vulgaris, neuromyelitis optica, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, sarcoidosis, giant cell arteritis, amyotrophic lateral sclerosis, Harada disease, autoimmune optic neuropathy, idiopathic azoospermia, habitual abortion, inflammatory bowel disease, celiac disease, ankylosing spondylitis, severe asthma, chronic urticarial, transplantation immunity, familial mediterranean fever, eosinophilic chronic rhinosinusitis, dilated cardiomyopathy, systemic mastocytosis, or inclusion body myositis.
34. The use according to claim 32 or 33, wherein the medicament is to be administered together with one or more agent(s) selected from an insulin formulation, sulfonylurea agent, quick-acting insulin secretion promoter, biguanide preparation, insulin resistance improving agent, a-glucosidase inhibitor, diabetic neuropathy therapeutic agent, GLP-1 analog preparation, and DPP-4 inhibitor, steroid agent, interferon ß-1a, interferon ß-1b, glatiramer acetate, mitoxantrone, azathioprine, cyclophosphamide, cyclosporin, methotrexate, cladribine, adrenocorticotropic hormone (ACTH), corticotropin, mizoribine, tacrolimus, fingolimod, alemtuzumab, immunosuppressive agent, belimumab, anti-rheumatic drug, anti-cytokine drug, and abatacept.
35. Use of the PD-1/CD3 bispecific antibody or antibody fragment thereof according to any one of claims 1 to 30 in the manufacture of a medicament for preventing, suppressing symptom progression or recurrence of, and/or treating graft-versus-host disease (GVHD).
36. The PD-1/CD3 bispecific antibody or antibody fragment thereof according to claim 1, substantially as herein described with reference to any one of the Examples and/or
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2018021498 | 2018-02-09 | ||
| JP2018153149 | 2018-08-16 | ||
| PCT/JP2019/004551 WO2019156199A1 (en) | 2018-02-09 | 2019-02-08 | Bispecific antibody |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ761547A NZ761547A (en) | 2023-11-24 |
| NZ761547B2 true NZ761547B2 (en) | 2024-02-27 |
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