Multimer of extracellular domain of cell surface functional molecule

• US 8,216,996 B2
• Filed: 03/02/2007
• Issued: 07/10/2012
• Est. Priority Date: 03/03/2006
• Status: Active Grant

• Current Assignee: ONO Pharmaceutical Company Limited
• Original Assignee: ONO Pharmaceutical Company Limited
• Inventors: Minato, Nagahiro, Shibayama, Shiro, Tanaka, Yoshimasa
• Primary Examiner(s): Noakes, Suzanne M
• Application Number:
  US12/281,427
• Publication Number:
  US 20090305950A1
• Time in Patent Office: 1,957 Days
• Field of Search: None
• US Class Current: 514/1.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 13/12 of the kidneys
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/06 for tuberculosis
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 33/08 : for Pneumocystis carinii
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: C07K 14/70503 : Immunoglobulin superfamily
• CPC Class Codes: C07K 14/70532 : B7 molecules, e.g. CD80, CD86
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

As a substance which pharmacologically regulates the function of a cell surface functional molecule, a substance which has specificity and an activity or efficacy equal or superior to an antibody and does not require an advanced production technique and facility for application thereof to a pharmaceutical product has been demanded. The invention relates to a multimer of an extracellular domain of a cell surface functional molecule, particularly a tetramer of an extracellular domain of PD-1 or PD-L1. Further, the invention relates to an application of such a tetramer as a preventive and/or therapeutic agent for cancer, cancer metastasis, immunodeficiency, an infectious disease or the like and an application of PD-1 or PD-L1 as a testing or diagnostic agent or a research agent for such a disease.

Claims

1. A multimer comprising four extracellular domains of Programmed Cell Death-1 (PD-1), wherein each of said four extracellular domains comprise a region selected from (a) and (b):

(a) residues 1-167 or residues 25-145 of full-length human PD-1, wherein the cysteine at position 93 is substituted by serine; and

(b) residues 1-169 or residues 25-145 of full-length mouse PD-1, wherein the cysteine at position 83 is substituted by serine,

and wherein said four extracellular domains are (i) serially-concatenated directly or with a peptide linker, or (ii) bound to a carrier via a non-peptide linker.

2. The multimer according to claim 1, wherein each of the four extracellular domains of PD-1 is serially-concatenated with peptide linkers.

3. The multimer according to claim 2, wherein each of the peptide linkers comprises 2 to 15 amino acids.

4. The multimer according to claim 3, comprising the amino acid sequence of SEQ ID NO:

1 or 3.

5. A pharmaceutical composition comprising the multimer according to claim 1 as an active ingredient.

6. The pharmaceutical composition according to claim 5, which is a preventive and/or therapeutic agent for cancers, cancer metastasis, immune deficiency syndrome or infectious diseases.

7. An agent comprising the multimer according to claim 1 and at least one ingredient selected from the group consisting of chemotherapy drugs, cancer treatment adjuvants, immunomodulators, cancer antigens, antiviral agents, antibiotic preparations, antimicrobials, fungal treatments and vaccines.

8. A Programmed Cell Death-Ligand 1 detection reagent comprising the multimer according to claim 1.

9. The multimer according to claim 1, wherein the carrier is an avidin, streptavidin or a derivative thereof and the non-peptide linker is a biotin.