Norwegian University of Science and Technology

Apim Therapeutics as

Protan Biopolymer A/s

Nobipols Forskningsstiftelse

Neocrin Company

Marit Otterlei

Terje Espevik

Siri Bachke

Per Arne Aas

Emadoldin Feyzi

Gudmund Skjak-Braek

Olav Smidsrod

Patrick Soon-Shiong

Gudmund Skjak-Brock

Olay Smidsrod

Per Aas

The present invention provides an agent, or a composition containing an agent, for use in treating or preventing a bacterial infection in a subject, wherein said agent comprises: In certain aspects the agent and compositions of the invention may be used as single agents. In other aspects of the invention agents and compositions of the invention may be used in conjunction with one or more additional active agents, such as antibiotics.

Antimicrobial agents and their use in therapy

The present invention provides an agent, or composition containing an agent, for use in treating or preventing hypercytokinemia in a subject resulting from cytokine release from non-proliferating immune cells in blood, wherein the agent comprises: (i) an oligopeptidic compound comprising a PCNA interacting motif and a domain that facilitates the cellular uptake of said compound, wherein the PCNA interacting motif is XXXXX(SEQ ID NO:) and wherein: Xis a basic amino acid; Xis an aromatic amino acid; Xis an uncharged amino acid other than an aromatic amino acid, Glycine (G) and Proline (P); Xis any amino acid other than Proline (P), an acidic amino acid or an aromatic amino acid; and Xis a basic amino acid or Proline (P); or (ii) a nucleic acid molecule comprising a sequence encoding the oligopeptidic compound of (i). In certain aspects the agent and compositions of the invention may be used as single agents. In other aspects of the invention agents and compositions of the invention may be used in conjunction with one or more additional active agents, such as kinase inhibitors.

Immunosuppressive agents and their use in therapy

The present invention provides an agent, or a composition containing an agent, for use in treating or preventing a bacterial infection in a subject, wherein said agent comprises: (i) an oligopeptidic compound comprising a PCNA interacting motif and a domain that facilitates the cellular uptake of said compound, wherein the PCNA interacting motif is XXXXXX(SEQ ID NO: 1) and wherein: Xis a basic amino acid; Xis an aromatic amino acid; Xis an aromatic amino acid or a hydrophobic amino acid that has an R group comprising at least three carbon atoms; Xis an uncharged amino acid other than an aromatic amino acid, Glycine (G) and Proline (P); Xis any amino acid other than an acidic amino acid or an aromatic amino acid; and Xis any amino acid other than an acidic amino acid or an aromatic amino acid, preferably a basic amino acid or Proline (P), wherein when Xis not an aromatic amino acid, Xis not lysine (K) and Xis a basic amino acid or Proline (P); or (ii) a nucleic acid molecule comprising a sequence encoding the oligopeptidic compound of (i). In certain aspects the agent and composition of the invention may be used as single agents. In other aspects of the invention the agents and composition may be used in conjunction with one or more addition active agents, such as antibiotics, or in combination with UV radiation.

Anti-bacterial agents and their use in therapy

The present invention provides an agent, or composition containing an agent, for use in treating or preventing hypercytokinemia in a subject resulting from cytokine release from non-proliferating immune cells in blood, wherein the agent comprises: In certain aspects the agent and compositions of the invention may be used as single agents. In other aspects of the invention agents and compositions of the invention may be used in conjunction with one or more additional active agents, such as kinase inhibitors.

Disclosed is A method of treatment of a disorder or condition where it is desirable to inhibit the growth of cells, or a method of treatment which involves cytostatic therapy by administering an oligopeptidic compound to a subject in need thereof. The oligopeptidic compound is capable of interacting with proliferating cell nuclear antigen (PCNA) The compound comprises a PCNA interacting motif which is: which is: [K/R]-[F/Y/W]-[L/I/V/A/M]-[L/I/V/A/M]-[K/R] (SEQ ID NO. 28). The oligopeptidic compound has 9-70 subunits and at least one signal sequence. The signal sequence is a nuclear localization signal sequence and/or a cell penetrating signal sequence. In the compound a PCNA interacting motif is N-terminal to a signal sequence.

Oligopeptidic compounds and uses thereof

Disclosed is an oligopeptidic compound capable of interacting with proliferating cell nuclear antigen (PCNA), wherein the compound comprises a PCNA interacting motif which is: wherein the oligopeptidic compound has 9-70 subunits and comprises at least one signal sequence, wherein the signal sequence is a nuclear localization signal sequence and/or a cell penetrating signal sequence and wherein in said compound a PCNA interacting motif is N-terminal to a signal sequence. Also disclosed are methods of treatment of a disorder or condition where it is desirable to inhibit the growth of cells, or a method of treatment which involves cytostatic therapy, or a method of treatment of inflammation said method comprising administering the oligopeptidic compound to a subject in need thereof.

The present invention provides an oligopeptidic compound comprising a PCNA interacting motif, or a nucleic acid molecule comprising a sequence encoding said oligopeptidic compound, for use in therapy, wherein the PCNA interacting motif is XXXXX- (SEQ ID NO: 1), wherein Xand X- are independently selected from the group of basic amino acids, Xis a lipophilic amino acid and Xand Xare independently selected from the group of uncharged amino acids; and wherein the oligopeptidic compound is further characterized by at least one of the following: (i) the oligopeptidic compound comprises at least one signal sequence; (ii) the PCNA interacting motif is [K/R]-F-[L/I/V]-[L/I/V]-[K/R] (SEQ ID NO: 27). Particularly the therapy may be the treatment of a disorder or condition where it is desirable to inhibit the growth of cells, for example a hyperproliferative disorder, or a treatment which involves cytostatic therapy e.g., myeloablation. In certain aspects the compounds of the invention may be used as cytostatic agents in their own right. In other aspects of the invention oligopeptidic compounds comprising such a motif may be used in conjunction with cytostatic agents or with radiotherapy.

Cells such as mammalian or genetically modified cells are encapsulated in high-G alginate that provokes reduced immune response during transplantation or implantation. The alginate contains greater than 50% .alpha.-L-guluronic acid and a minimal amount of mannuronic acid. The amount of .alpha.-L-guluronic acid is preferably at least 65% and more preferably at least 85%. Encapsulation is carried out by suspending cells in a solution of the high-G alginate, forming drops of the solution and contacting the drops with calcium ions to gel the alginate and form microcapsules containing the cells. The microcapsules may contain multiple layers with the high-G alginate preferably forming the outermost layer.

Cells encapsulated in alginate containing a high content of a- l-

The present invention is directed to a material and method for the stimulation of the production of cytokines. Several polysaccharides, including polymers of different size of .sym.1-4 linked D-mannuronic acid (poly-M and M-blocks), chitosan and cellulose oxidized in C-6 position C60XY) induce human monocytes to produce the cytokines. Preferably, the molecular weights of poly-M and chitosan are above 50,000 and 20,000 respectively. Pretreatment of the monocytes with IFN-.gamma. increases the cytokine production from monocytes stimulated with all polysaccharides tested. The subject polysaccharides worked in vivo and in vitro. The present invention has therapeutic utility as vaccine adjuvants and components. Therapeutic compositions comprising biologically active quantities of the compositions of the present invention may be employed to potentiate antibody production in response to vaccine antigens. Anti-tumor, anti-bacteriological, anti-fungal and anti-viral effects may be expected.

Diequatorially bound .beta.-1, 4 polyuronates and use of same for

A family of compounds effective in inhibiting interleukin-1 (IL-1) production, interleukin-6 (IL-6), tumor necrosis factor (TNF) production, and the production of other leukocyte derived cytokines is comprised of oligomers and polymers of .alpha.1-4 linked L-guluronic acid residues which may be administered to a human or mammal in an amount sufficient to inhibit the production effect of leukocyte-derived cytokines. The inhibition of IL-1, IL-6 and TNF, and other cytokines in mammals is implicated in alleviation of a wide variety of disease conditions.

Growing community of inventors

Trondheim, Norway

Marit Otterlei