# US 2014/0193396 A1 · Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response

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- Number: US 2014/0193396 A1
- Document ID: US20140193396A1
- Status: Published application
- Kind: A1
- Application number: 14/149,899
- Filed: 2014-01-08
- Published: 2014-07-10
- Earliest claimed: 2013-01-08
- Assignees: Idera Pharmaceuticals, Inc.
- Applicants: Idera Pharmaceuticals, Inc.
- Inventors: Ekambar R. Kandimalla; Daqing Wang; Dong Yu; Ireneusz Nowak; Sudhir Agrawal
- Web page: https://patentgrep.com/patent/US20140193396A1

## CPC

- C12N 15/117: Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
- 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)}
- A61K 31/711: Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
- A61K 31/7115: Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 5/14: of the thyroid hormones, e.g. T3, T4
- A61P 7/06: Antianaemics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/08: of the prostate
- A61P 13/10: of the bladder
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 17/14: for baldness or alopecia
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants}
- C12N 2310/17: Immunomodulatory nucleic acids
- C12N 2310/3341: 5-Methylcytosine
- C12N 2310/335: Modified T or U
- C12N 2310/336: Modified G
- C12N 2320/30: Special therapeutic applications
- C12N 2320/31: Combination therapy
- C12N 2710/24043: viral genome or elements thereof as genetic vector
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The invention provides immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.

## Claims

### Claim 1

An immune regulatory oligonucleotide (IRO) compound selected from 5′-C*TATC*TGUC*G1TTC*TC*TGU-3′ and 5′-CTATCTGUC*G2TTCTCTGU-3′, wherein G1=7-deaza-dG; C*=5-Me-dC; G=2’-O-Me-G; U=2′-O-Me-U; and G2=AraG.

### Claim 2 (depends on 1)

A pharmaceutical composition comprising an IRO according to claim 1 and a pharmaceutically acceptable carrier.

### Claim 3 (depends on 1)

A method for inhibiting a TLR9-, TLR7-, and/or TLR8-mediated immune response in a mammal, the method comprising administering to the mammal an IRO according to claim 1 or a composition thereof.

### Claim 4 (depends on 3)

The method according to claim 3, wherein the route of administration is parenteral, mucosal delivery, oral, sublingual, transdermal, topical, inhalation, intranasal, aerosol, intraocular, intratracheal, intrarectal, vaginal, by gene gun, dermal patch or in eye drop or mouthwash form.

### Claim 5 (depends on 3)

The method according to claim 3, wherein the mammal is a human.

### Claim 6 (depends on 3)

The method according to claim 3, wherein the IRO is administered in combination with one or more vaccines, antigens, antibodies, cytotoxic agents, allergens, antibiotics, antisense oligonucleotides, TLR antagonists, peptides, proteins, gene therapy vectors, DNA vaccines, adjuvants, or kinase inhibitors.

### Claim 7 (depends on 1)

A method for inhibiting the activity of a TLR9, TLR7, and/or TLR8 agonist comprising administering an IRO according to claim 1 or a composition thereof.

### Claim 8 (depends on 7)

The method according to claim 7, comprising administering the IRO prior to or at the same time as the TLR9, TLR7, and/or TLR8 agonist.

### Claim 9 (depends on 1)

A method for therapeutically treating a mammal having an autoimmune disease mediated by TLR9, TLR7, and/or TLR8, comprising administering to the mammal an IRO according to claim 1 or a composition thereof.

### Claim 10 (depends on 9)

The method according to claim 9, wherein the autoimmune disease is selected from psoriasis, rheumatoid arthritis, alopecia universalis, acute disseminated encephalomyelitis, Addison's disease, ankylosing spondylitis, antiphospholipid antibody syndrome, autoimmune hemolytic anemia, autoimmune hepatitis, Bullous pemphigoid, chagas disease, chronic obstructive pulmonary disease, coeliac disease, dermatomyositis, endometriosis, Goodpasture's syndrome, Graves' disease, Guillain-Barré syndrome, Hashimoto's disease, hidradenitis suppurativa, idiopathic thrombocytopenic purpura, interstitial cystitis, morphea, myasthenia gravis, narcolepsy, neuromyotonia, pemphigus, pernicious anaemia, polymyositis, primary biliary cirrhosis, schizophrenia, Sjögren's syndrome, temporal arteritis, vasculitis, vitiligo, vulvodynia and Wegener's granulomatosis.

### Claim 11 (depends on 9)

The method according to claim 9, wherein the antagonist is administered in combination with one or more vaccines, antigens, antibodies, cytotoxic agents, allergens, antibiotics, antisense oligonucleotides, TLR antagonists, peptides, proteins, gene therapy vectors, DNA vaccines, adjuvants, kinase inhibitors.

### Claim 12 (depends on 9)

The method according to claim 9, wherein the route of administration is parenteral, mucosal delivery, oral, sublingual, transdermal, topical, inhalation, intranasal, aerosol, intraocular, intratracheal, intrarectal, vaginal, by gene gun, dermal patch or in eye drop or mouthwash form.

### Claim 13 (depends on 9)

The method according to claim 9, wherein the mammal is a human.

### Claim 14 (depends on 1)

A method for preventing an autoimmune disease mediated by a TLR9, TLR7, and/or TLR8, comprising administering to a mammal an IRO according to claim 1 or a composition thereof.

### Claim 15 (depends on 14)

The method according to claim 14, wherein the autoimmune disease is selected from psoriasis, rheumatoid arthritis, alopecia universalis, acute disseminated encephalomyelitis, Addison's disease, ankylosing spondylitis, antiphospholipid antibody syndrome, autoimmune hemolytic anemia, autoimmune hepatitis, Bullous pemphigoid, chagas disease, chronic obstructive pulmonary disease, coeliac disease, dermatomyositis, endometriosis, Goodpasture's syndrome, Graves' disease, Guillain-Barré syndrome, Hashimoto's disease, hidradenitis suppurativa, idiopathic thrombocytopenic purpura, interstitial cystitis, morphea, myasthenia gravis, narcolepsy, neuromyotonia, pemphigus, pernicious anaemia, polymyositis, primary biliary cirrhosis, schizophrenia, Sjögren's syndrome, temporal arteritis, vasculitis, vitiligo, vulvodynia or Wegener's granulomatosis.

### Claim 16 (depends on 14)

The method according to claim 14, wherein the antagonist is administered in combination with one or more vaccines, antigens, antibodies, cytotoxic agents, allergens, antibiotics, antisense oligonucleotides, TLR antagonists, peptides, proteins, gene therapy vectors, DNA vaccines, or adjuvants.

### Claim 17 (depends on 14)

The method according to claim 14, wherein the route of administration is parenteral, mucosal delivery, oral, sublingual, transdermal, topical, inhalation, intranasal, aerosol, intraocular, intratracheal, intrarectal, vaginal, by gene gun, dermal patch or in eye drop or mouthwash form.

### Claim 18 (depends on 14)

The method according to claim 14, wherein the mammal is a human.

### Claim 19 (depends on 2)

The composition according to claim 2, further comprising one or more vaccines, antigens, antibodies, cytotoxic agents, allergens, antibiotics, antisense oligonucleotides, TLR antagonists, peptides, proteins, gene therapy vectors, DNA vaccines, or adjuvants.

### Claim 20 (depends on 1)

A composition comprising an antagonist according to claim 1 and one or more vaccines, antigens, antibodies, cytotoxic agents, allergens, antibiotics, antisense oligonucleotides, TLR antagonists, peptides, proteins, gene therapy vectors, DNA vaccines, or adjuvants.