Statens Serum Institut

Pharmexa A/s

Other

Institut Pasteur

H. Lundbeck A/s

Bn Immunotherapeutics, Inc.

Bavarian Nordic A/s

Peter Birk Rasmussen

Peter Andersen

Klaus Gregorius Nielsen

Karin Weldingh

Walter Florio

Lucilla Steinaa

Søren Mouritsen

Martin Roland Jensen

Iben Dalum

Dana Leach

Anand Gautam

Gunilla Karlsson

Rikke Louise Vinther Skjot

Li Mei Meng Okkels

Christina Veggerby Hansen

Brigitte Gicquel

Ida Rosenkrands

Anja Olsen

Francois-Xavier Berthet

Willem Adriaan De Jongh

Jesper Haaning

Soren Mouritsen

Rikke Louise Vinther Skjøt

Thomas Oettinger

Peter Koefoed

Florence Dal Degan

Jesper Hanning

Rikke Nielsen

Disclosed are novel methods and compositions for combating diseases characterized by deposition of amyloid. The methods generally rely on immunization against amyloid precursor protein (APP) or beta amyloid (A&#x3b2;). Immunization is preferably effected by administration of analogs of autologous APP or A&#x3b2;, said analogs being capable of inducing antibody production against the autologous amyloidogenic polypeptides. Especially preferred as an immunogen is autologous A&#x3b2; which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes. Such methods and means include methods for the preparation of analogs and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations.

Amyloid-beta polypeptide vaccine

The present invention provides a method for combining the advantages of encoded molecule fragments made by split and mix synthesis with the advantages of template directed synthesis of molecules. The method provided in the invention comprises the steps of: Adding a linker molecule L to one or more reaction wells; Adding a molecule fragment to each of said reaction wells; Adding an oligonucleotide identifier to each of said reaction wells; Subjecting said wells to conditions sufficient to allow said molecule fragments and said oligonucleotie identifiers to become attached to said linker molecule, or conditions sufficient for said molecule fragments to bind to other molecule fragments and sufficient for said oligonucleotide identifiers to bind to other oligonucleotide identifiers; Combining the contents of said one or more reaction wells; Optionally, distributing the combined product to one or more new reaction wells; Optionally, repeating steps b) to e) one or more times; Contacting the resulting bifunctional molecule(s) of step e) or g) with one or more Contacting the resulting bifunctional molecule(s) of step e) or g) with one or more (oligonucleotide) templates each capable of hybridizing to at least one of the oligonucleotide identifiers added in step c).

Template directed split and mix systhesis of small molecule libraries

The present invention is based on the identification and characterization of a number of novelderived proteins and protein fragments. The invention is directed to the polypeptides and immunologically active fragments thereof, the genes encoding them, immunological compositions such as diagnostic reagents containing the polypeptides.

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A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells are disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.

Methods for therapeutic vaccination

A method for in vivo down-regulation of amyloid protein in an animal, including a human being, the method comprising effecting presentation to the animal's immune system of an immunogenically effective amount of at least one amyloidogenic polypeptide or subsequence thereof which has been formulated so that immunization of the animal with the amyloidgenic polypeptide or subsequence thereof induces production of antibodies against the amyloidogenic polypeptide, and/or at least one analogue of the amyloidogenic polypeptide wherein is introduced at least one modification in the amino acid sequence of the amyloidogenic polypeptide which has as a result the immunization of the animal with the analogue induces production of antibodies against the amyloidogenic polypeptide.

Method for down-regulation of amyloid

The present invention discloses fusion proteins of the immunodominant antigens ESAT-6 and Ag85B fromor homologues thereof, and a tuberculosis vaccine based on the fusion proteins, which vaccine induces efficient immunological memory.

Hybrids of M. tuberculosis antigens

A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8b. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8b, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells are disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.

TB diagnostic based on antigens from M. tuberculosis

The present invention is based on the identification and characterization of a number of derived novel proteins and protein fragments (SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 17-23, 42, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72-86, 88, 90, 92, 94, 141, 143, 145, 147, 149, 151, 153, and 168-171). The invention is directed to the polypeptides and immunologically active fragments thereof, the genes encoding them, immunological compositions such as vaccines and skin test reagents containing the polypeptides. Another part of the invention is based on the surprising discovery that fusions between ESAT-6 and MPT59 are superior immunogens compared to each of the unfused proteins, respectively.

Nucleic acids fragments and polypeptide fragments derived from M. tuberculosis

The present invention is directed to a polynucleotide carrying an open reading frame coding for an antigenic polypeptide from named lhp, which is placed under the control of its own regulation signals which are functional in mycobacteria, specially in mycobacteria belonging to the complex and also in fast growing mycobacteria such as The invention is also directed to the polypeptide LHP encoded by lhp and most preferably to suitable antigenic portions of LHP as well as to oligomeric polypeptides containing more than one unit of LHP or an antigenic portion of LHP. The invention concerns also immunogenic and vaccine compositions containing a polypeptide or an oligomeric polypeptide such as defined above, as well as antibodies directed specifically against such polypeptides that are useful as diagnostic reagents. In another embodiment, the present invention is directed to a polynucleotide carrying the natural regulation signals of lhp which is useful in order to express heterologous proteins in mycobacteria. Finally, the present invention is directed to oligonucleotides comprising at least 12 consecutive nucleotides from the regulation sequence of lhp which are useful as reagents for detecting the presence of in a biological sample.

Polynucleotide functionally coding for the LHP protein from Mycobacterium tuberculosis, its biologically active derivative fragments, as well as methods using the same

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Frederiksberg, Denmark

Peter Birk Rasmussen