Substance specific to human PD-1

• US 7,998,479 B2
• Filed: 05/20/2009
• Issued: 08/16/2011
• 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: Shibayama, Shiro, Yoshida, Takao, Miyamoto, Masakazu, Takeda, Kazuhiko, Honjo, Tasuku, Matsuo, Masayoshi
• Primary Examiner(s): OUSPENSKI, ILIA I
• Application Number:
  US12/469,188
• Publication Number:
  US 20090263865A1
• Time in Patent Office: 818 Days
• Field of Search: None
• US Class Current: 424/130.1
• 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 insulin dependent diabetes mellitus, comprising administering an effective amount of a bispecific antibody to an insulin dependent diabetes mellitus patient, wherein the bispecific antibody comprises the following parts:

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

(b) VL region of anti-human CD3ε

antibody;

(c) VH region of said anti-human CD3ε

antibody; and

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

and wherein said each part is linked by peptide linkers in the above order, so that said part (a) can bind to human PD-1 together with said part (d) and said part (c) can bind to human CD3ε

together with said part (b).

2. The preventive and/or 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 CD3ε

antibody is a polypeptide comprising the amino acid sequence of SEQ ID NO;

8,

(c) the VH region of said anti-human CD3ε

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.