Index Pharmaceuticals Ab

Arezou Zargari

Oliver Von Stein

Charlotte Admyre

Petra Von Stein

Lars-Göran Axelsson

Lars-Goran Axelsson

Robert Löfberg

Lisa Charlotta Bandholtz

Peter Zerhouni

Ann-Kristin Spiik

Thomas Knittel

Nicolai Kouznetzov

Pernilla Sandwall

Nikolai Kouznetsov

Alexander Gielen

Asa Karlsson

Nikolai Kouznetzov

Robert Lofberg

The present invention provides an oligonucleotide comprising the sequence 5'-GGAACAGTTCGTCCATGGC-3&#x2032; (SEQ ID NO:2) for use in the treatment of inflammatory bowel disease in a human subject, wherein individual doses of from 100 mg to 350 mg of said oligonucleotide are administered to the subject on at least four separate occasions, wherein the separate occasions are each a week apart.

Therapy

The present invention provides an oligonucleotide comprising the sequence 5'-GGAACAGTTCGTCCATGGC-3&#x2032; (SEQ ID NO:2) for use in the treatment of inflammatory bowel disease in a human subject, wherein individual doses of from 150 mg to 350 mg of said oligonucleotide are administered to the subject on at least two separate occasions, wherein said separate occasions are 3 weeks apart.

Cobitolimod for use in the treatment of inflammatory bowel disease

Methods for reducing recruitment, migration, or both recruitment and migration of polymorphonuclear cells to a site of inflammation in an organ of a human patient comprise administering locally to the organ or systemically to the patient in need thereof an isolated oligonucleotide selected from the group consisting of SEQ ID NO: 8 (IDX9059); SEQ ID NO: 14 (IDX9052); SEQ ID NO: 7 (IDX9054); SEQ ID NO: 6 (IDX9045); SEQ ID NO: 1 (IDX9005); SEQ ID NO: 9 (IDX9074); SEQ ID NO: 3 (IDX9022); SEQ ID NO: 2 (IDX9010); SEQ ID NO: 4 (IDX9030); and SEQ ID NO: 13 (IDX0150).

Compounds and methods for reducing the recruitment and/or migration of polymorphonuclear cells

A method of treating chronic active ulcerative colitis in a subject that is refractory or responds insufficiently or is intolerant to anti-inflammatory therapy, comprises administering to a patient in need thereof an effective exposure of an oligonucleotide comprising the sequence 5'-GGAACAGTTCGTCCATGGC-3&#x2032; (SEQ ID NO.2), wherein at least one CG dinucleotide is unmethylated. The oligonucleotide is not administered with corticosteroids or glucocorticosteroids.

Method for prevention of colectomy

The present invention relates to methods of identifying oligonucleotides capable of modulating the immune system in a mammalian subject, comprising analysis of which tertiary structural type said oligonucleotide adopts, in phosphate-buffered saline solution. Further, the invention provides oligonucleotides identifiable by the methods of the invention and to their use in methods of treating diseases, such as inflammatory diseases, autoimmune diseases, infectious diseases, neurodegenerative diseases and cancer.

Method for identifying biologically active oligonucleotides capable of modulating the immune system

The present invention relates to methods of preventing or reducing the need of colectomy. In particular, the present invention relates to an oligonucleotide, for use in the treatment of an inflammatory bowel disease, such as ulcerative colitis (UC) or Crohn's disease, in a subject that is refractory or responds insufficiently or is intolerant to anti-inflammatory therapy, wherein said oligonucleotide is repetitively administered as a single exposure.

A therapeutically effective amount of an oligonucleotide is capable of influencing the properties and behavior of polymorphonuclear cells, e.g. suppressing endothelial adhesion and transmigration of said cells, and through this mechanism reduce the recruitment and/or migration of polymorphonuclear cells to a site of inflammation.

Inflammatory diseases in the CNS can be treated or alleviated by the administration of an oligonucleotide in an amount sufficient to reduce the influx of mononuclear cells to the central nervous system by down-regulating the expression of at least one cell surface marker. For example multiple sclerosis can be treated or at least alleviated, by the administration of an oligonucleotide in a dose effective to inhibit or reduce the influx of mononuclear and/or autoaggressive cells to the central nervous system. The oligonucleotide can be used alone, or in combination with other treatment strategies.

Compounds and methods for the treatment of inflammatory diseases of the CNS

Methods for enhancing steroid efficacy in a steroid refractory patient afflicted with an inflammatory condition who does not respond or responds poorly or inadequately to steroid anti-inflammatory treatment or a steroid dependent patient afflicted with an inflammatory condition and currently on steroid anti-inflammatory treatment who shows an inability to be weaned off systemic or topical administered steroid treatment comprise administering an oligonucleotide having the sequence 5'-X-CG-Y-3&#x2032; wherein X is A, T, C, or G, Y is A, T, C, or G, m is 1-20 and n is 1-20, or the sequence 5&#x2032;-CG-3&#x2032; and from 8 to 40 nucleotides, wherein at least one CG dinucleotide is unmethylated. The oligonucleotide is administered in an amount effective to improve sensitivity of the patient to the steroid anti-inflammatory treatment and thereby induce a clinical response in the steroid refractory patient or improve a clinical response in the steroid dependent patient.

Immunostimulatory method

A method for enhancing steroid efficacy in a steroid refractory patient afflicted with an inflammatory condition not responding or responding poorly or inadequately to anti-inflammatory treatment comprises administering an oligonucleotide having the sequence formula in an effective amount to said patient and wherein X is A, T, C or G, Y is A, T, C or G, m=0-7, n=0-7 and wherein at least one CG dinucleotide is unmethylated.

Method for modulating responsiveness to steroids

Isolated and substantially purified oligonucleotide compounds have been shown to be effective in reducing swelling and edema. Novel methods and substances are presented for the prevention, alleviation or treatment of edema of various aetiology.

Compounds for the treatment or alleviation of edema, and methods for their use

Specific CpG oligonucleotide sequences, when given subcutaneously and in particular when administered on a mucous membrane, e.g. intranasally, intravaginally, or rectally, have a profound effect on various human cancer forms as confirmed in vivo, in animal studies, and in vitro, in human PBMCs collected from blood from healthy subjects and from patients suffering from CLL or FL. The compounds are also preferably used in combination with a cancer therapy chosen among radiation treatment, hormone treatment, surgical intervention, chemotherapy, immunological therapies, photodynamic therapy, laser therapy, hyperthermia, cryotherapy, angiogenesis inhibition, or a combination of any of these, and is most preferably an immunological treatment and comprises the administration of an antibody to the patient.

Growing community of inventors

Solna, Sweden

Arezou Zargari