Substance specific to human PD-1

• US 8,246,955 B2
• Filed: 06/27/2011
• Issued: 08/21/2012
• Est. Priority Date: 01/23/2003
• Status: Active Grant

• Current Assignee: ONO Pharmaceutical Company Limited, Tasuku Honjo
• Original Assignee: ONO Pharmaceutical Company Limited, Tasuku Honjo
• Inventors: Honjo, Tasuku, Shibayama, Shiro, Matsuo, Masayoshi, Takeda, Kazuhiko, Yoshida, Takao, Miyamoto, Masakazu
• Primary Examiner(s): OUSPENSKI, ILIA I
• Application Number:
  US13/169,278
• Publication Number:
  US 20110280878A1
• Time in Patent Office: 421 Days
• Field of Search: None
• US Class Current: 424/136.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/2803 : against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2809 : against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2818 : against CD28 or CD152
• CPC Class Codes: C07K 2317/31 : multispecific
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

Abstract

The present invention relates to a substance specific to human PD-1 comprising a part that recognizes human PD-1, a part that recognizes a membrane protein in cell membrane of human PD-1-expressing cells, and linkers. Since the substance specific to human PD-1 selectively can recognize human PD-1 and a membrane protein on cell membrane of human PD-1-expressing cells and can transmit inhibitory signal of human PD-1, it is useful for therapy and/or prevention of diseases caused by immunopathy.

Claims

1. A therapeutic method for autoimmune disease, comprising administering an effective amount of a bispecific antibody to an autoimmune disease patient, wherein the bispecific antibody comprises the following parts:

(a) VH region of anti-human PD-1 antibody;

(b) VL region of anti-human CD3 antibody;

(c) VH region of said anti-human CD3 antibody; and

(d) VL region of said anti-human PD-1 antibody,

and wherein each of said parts is linked by peptide linkers, so that said part (a) can bind to human PD-1 together with said part (d) and said part (c) can bind to human CD3 together with said part (b), and the autoimmune disease is a disease selected from ulcerative colitis, Sjorgen'"'"'s syndrome, Crohn'"'"'s disease, systemic lupus erythematosus, chronic rheumatoid arthritis, multiple sclerosis, psoriasis, polymyositis, periarteritis nodosa, rheumatic fever, Behcet'"'"'s disease, Hashimoto'"'"'s disease, dermatomyositis, myasthenia gravis, Reiter'"'"'s syndrome, Graves'"'"' disease, Goodpasture'"'"'s syndrome, pemphigus, autoimmune thrombocytopenic purpura, and autoimmune hemolytic anemia.

2. The therapeutic method according to claim 1, wherein said human CD3 is human CD3 epsilon.

3. The therapeutic method according to claim 1, wherein parts (a)-(d) of claim 1 are linked by peptide linkers in alphabetical order, respectively.

4. The therapeutic method according to claim 1, wherein

(a) the VH region of anti-human PD-1 antibody is a polypeptide comprising the amino acid sequence of SEQ ID NO:

2,

(b) the VL region of anti-human CD3 antibody is a polypeptide comprising the amino acid sequence of SEQ ID NO;

8,

(c) the VII region of said anti-human CD3 antibody is a polypeptide comprising the amino acid sequence of SEQ ID NO;

6 and

(d) the VL region of said anti-human PD-1 antibody is a polypeptide comprising the amino acid sequence of SEQ ID NO;

4.

5. The therapeutic method according to claim 1, wherein the autoimmune disease is a disease selected from ulcerative colitis, Crohn'"'"'s disease, systemic lupus erythematosus and multiple sclerosis.