Index Pharmaceuticals Ab

Index Diagnostics Ab

Oliver Von Stein

Arezou Zargari

Charlotte Admyre

Petra Von Stein

Robert Löfberg

Lisa Charlotta Bandholtz

Lars-Göran Axelsson

Ann-Kristin Spiik

Nicolai Kouznetzov

Alexander Gielen

Lars-Goran Axelsson

Nikolai Kouznetsov

Karin Hellström

Asa Karlsson

Nikolai Kouznetzov

Andreas Dieckmann

Robert Lofberg

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 method for enhancing the clinical responsiveness to an anti-inflammatory therapy in a patient afflicted with an inflammatory condition, comprising administering an oligonucleotide having the sequence 5'-Xm-CG-Yn-3&#x2032; in an effective amount to said patient, and wherein X is A, T, C or G; Y is A, T, C or G; m=1-40; n=1-40 and wherein at least one CG dinucleotide is unmethylated. The invention also encompasses the use of such an oligonucleotide for the manufacture of a medicament for enhancing steroid efficacy in the treatment of a patient afflicted with an inflammatory condition.

Composition and method for the prevention, treatment and/or alleviation of an inflammatory disease

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

The invention concerns an in vitro method for selecting the therapy for a steroid resistant patient, wherein the method comprises isolating cells from a sample taken from said patient; cultivating said isolated cells in the presence of a steroid, an immunomodulatory oligonucleotide or a mixture thereof; determining an expression level of at least one marker gene in said isolated cells; and comparing said expression level of said at least one marker gene to a value obtained from the cultivation of cells from a healthy person in the presence of a steroid, an immunomodulatory oligonucleotide or a mixture thereof, or to a normalized value obtained from a healthy population. Examples of marker genes are CD163, Tsp1, IL1-R2, TLR2, TLR4, MKP-1 and TXK.

Method for predicting the response to a therapy

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

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.

Tumour growth inhibitory compounds and methods of their use

The present invention makes it possible to enhance steroid efficacy in a steroid refractory or dependent patient afflicted with an inflammatory condition not responding or responding poorly or inadequately to anti-inflammatory treatment, by administering an oligonucleotide having the sequence 5 5'-Xm-CG-Yn-3&#x2032; in an effective amount to said patient and wherein X is A, T, C or G, Y is A, T, C, or G, m=1-100, n=1-100 and wherein at least one CG dinucleotide is ummethylated. The invention also encompasses the use of said oligonucleotide for the manufacture of pharmaceuticals.

The present invention makes it possible to enhance steroid efficacy in a steroid refractory patient afflicted with an inflammatory condition not responding or responding poorly or inadequately to anti-inflammatory treatment, by administering an effective amount of an oligonucleotide having the sequence 5'-Xm-TTCGT-Yn-3&#x2032; to 5 said patient, 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. The invention also encompasses the use of said oligonucleotide for the manufacture of pharmaceuticals.

The differentiation between ulcerative colitis and Crohn's disease is made possible by a multi-gene approach where gene expression profiles in biopsy samples obtained from inflamed, and optionally also non-inflamed, areas in the intestines of a patient are studied.

Growing community of inventors

Upplands Väsby, Sweden

Oliver Von Stein