Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Other

Université Louis Pasteur

Bristol-myers Squibb Compnay

E. R. Squibb Sons, Inc.

Transgene S.a.

Institut Pasteur

University of Illinois

UniversitÉde Strasbourg

Université Louis Pasteur Strasbourg I

Gie-cerbm, Centre Europeen De Recherche En Biologie Et En Medecine (gie)

Gie-cerbn, Centre Europeen De Recherche En Biologie Et En Medecine (gie)

Association Pour Le Development De La Recherche En Genetique Moleculaire (aderegem)

Centre National De La Recherche Scientifique-cnrs

Pierre H Chambon

Daniel Metzger

Pierre Tiollais

Henri Cramail

Hinrich Gronemeyer

Philippe Kastner

Martin Petkovich

Manuel Mark

Marie-Paule Kieny

Richard Lathe

Nigel Brand

Andree Krust

Mara Hareuveni

Philippe Gorry

Thomas Lufkin

Jacek Ostrowski

Norbert B Ghyselinck

Huimin Zhao

Eric Cloutet

Agnes Marchio

Andree Dierich

Marianne Lemeur

Jean-Pierre Bellocq

Cathy Mendelsohn

David Lohnes

Anne Dejean

Peter R Reczek

Paul Basset

John White

John A Katzenellenbogen

Serge Ravaine

Yves Lutz

Johannes Voegel

Jean-Claude Nicolas

Hughes Blaudin De The

Mark Leid

Nigel J Brand

Marie-Christine Nee Martinet Rio

Marie-Pierre Gaub

Isabelle Scheuer

Michael Saunders

Cecille Rochette-Egly

Anne DeJean

Hughes B De The

Sylvie Roux

Val&eacute;rie Dup&eacute;

Jacques Bertrand Brocard

Emiliana Borrelli

Guoqiang Hua

Two enantiomers of a SElective Glucocorticoid Receptor Agonistic Modulator (SEGRAM) of Formula 1 or a derivative thereof; to a deuterated form of a SEGRAM of Formula 1 or a derivative thereof; and to the two deuterated enantiomers of a SEGRAM of Formula 1 or a derivative thereof: or a pharmaceutically acceptable salt, solvate and/or prodrug thereof. The present invention also relates to a SEGRAM of Formula 1 or a derivative thereof, or a pharmaceutically acceptable enantiomer, deuterated form, salt, solvate and/or prodrug thereof, for use in the prevention or treatment of an inflammatory disorder in a subject in need thereof.

Non-steroidal selective glucocorticoid receptor agonistic modulators (SEGRAMs) and uses thereof

The present invention relates to a method for tightly temporally controlling the biological activity of a protein of interest in a vertebrate, upon induction of the activity of a fusion protein comprising said protein of interest and an ERM polypeptide containing a mutated ligand binding domain of the human oestrogen receptor &#x3b1;, with a synthetic ligand that does not interfere with oestrogen signalling. In particular, the present invention concerns a method for generating tightly temporally-controlled targeted somatic mutations in a vertebrate, preferably a mouse, by inducing the activity of a fusion protein comprising a site-specific recombinase protein and an ERM polypeptide, with a synthetic ligand devoid of oestrogenic and anti-oestrogenic activities.

Method for controlling the biological activity of a protein in a vertebrate cell

The present invention relates to a metazoan organism, with the exception of humans, and in particular a mouse, characterized in that at least one cell of this organism comprises at least one fusion protein between a recombinase Cre and a modified ligand binding domain of the nuclear estrogen receptor alpha, allowing the inactive fused recombinase to be induced by synthetic antiestrogens, but not by natural estrogens, and one or more DNA sequences of interest belonging to the genome of said organism into which one or more sites of recognition of said recombinase protein are inserted. The invention also covers the methods using said organism for the screening of medicaments, the mutagenesis and the analysis of the biological function of the DNA sequences) of interest, in particular of gene(s) of interest, such as RXR.

Transgenic mouse for targeted recombination mediated by modified Cre-ER

The invention relates to a method for the stable inversion of a DNA fragment upon recombinase-mediated rearrangements using two sets of two incompatible site-specific recombinase targeting sites (SSRTS) in the same order but in reverse orientation flanking the DNA fragment to be inverted. The invention also relates to a method for the stable inversion of the DNA fragment upon rearrangement mediated by a recombinase such as Cre recombinase. The invention also relates to a method for obtaining a transgenic cell of which at least one allele of a DNA sequence of interest is invalidated by a process of conditional deletion and the genome of which has a reporter gene inserted at the place of the DNA fragment deleted by the process of conditional deletion. A method to generate targeting sites to perform site-specific recombination mediated cassette exchange is also provided.

Method for the stable inversion of DNA sequence by site-specific recombination and DNA vectors and transgenic cells thereof

The present invention concerns a nuclear receptor (NR) transcriptional mediator. More specifically, isolated nucleic acid molecules are provided encoding transcriptional intermediary factor-2 (TIF2). Recombinant methods for making TIF2 polypeptides are also provided as are TIF2 antibodies. Screening methods are also provided for identifying agonists and antagonists of the activation function AF-2 of nuclear receptors, for identifying agonists and antagonists of the AD1 activation domain activity of TIF2, and for identifying agonists and antagonists of the AD2 activation domain activity of TIF2.

Transcriptional intermediary factor-2

A DNA fragment coding for a modified nuclear glucocorticoid receptor, particularly one mutated in the region coding for the ligand binding domain, so that receptor activity is more strongly inducible by a synthetic glucocorticoid ligand than by a natural glucocorticoid ligand, is disclosed. A recombination system inducible in mammals by means of a fusion protein produced between a recombinase and the binding domain of the ligand derived from the modified glucocorticoid receptor of which the activity is more strongly inducible by synthetic glucocorticoids than by natural glucocorticoids, is also disclosed.

Modified nuclear glucocorticoid receptor, fusion protein, and DNA fragments coding for said receptor and said fusion protein

The present invention provides compositions and methods for treating an animal, preferably a human, suffering from or predisposed to a physical disorder by administering an effective amount of a composition comprising at least one RAR antagonist, preferably an RAR&agr; antagonist, and at least one RXR agonist. The combination of an RXR agonist, which has no therapeutic effects alone, with an RAR antagonist allows the use of lower doses of the RAR antagonist than were previously thought to be efficacious; this approach obviates many of the undesirable physiological side-effects of treatment with RAR antagonists.

Therapeutic combinations of RAR antagonists and RXR agonists and use thereof

The present invention is based in part on the novel observation that two different types of nuclear receptors, retinoic acid receptors (RAR) and thyroid receptors (TR) dimerize with a RX receptor (RXR) to form a heterodimer which is capable of binding to retinoic acid response elements (RARE) or thyroid receptor response elements (TRE) at physiological conditions. In addition, the present invention discloses that RXR homodimers are capable of binding to RARE's. Based on this observation, the present invention provides novel dimeric proteins, methods of identifying agents capable of binding the dimers of the present invention, methods of identifying DNA sequences capable of being bound by the dimers and methods to identify RA metabolic enzymes and proteins which are required for the activation function of nuclear receptors.

Heterodimeric nuclear receptors proteins, genes encoding same, and usage thereof

The invention relates to methods for treatment of neurological disease by administering an agent which interacts with a retinoid receptor associated with the neurological disease. The invention is also related to a method of modulating dopamine receptor synthesis by introducing an agent that interacts with a retinoid receptor associated with the dopamine receptor synthesis. The invention is further related to a transgenic animal, e.g., mouse, and mammalian cell line, which is deficient in the normal synthesis of one or more receptors of RAR&agr;, &bgr;, &ggr; and RXR, and cell line thereof.

Use of ligands for treatment of diseases responsive to retinoids

The present invention provides mice which are deficient in the normal expression of one or more members of the RAR or RXR class of receptors, to mice heterozygous for such deficiency, and to cell lines, preferably pluripotent or totipotent cell lines, which are heterozygous or homozygous for such deficiency. The present invention further provides the use of any of the above mice and cell lines in situations where the absence of at least one RAR or RXR receptors, or the normal expression thereof, is desirable.

Genetically engineered mice containing alterations in the genes encoding retinoic acid receptor proteins

The present invention relates to a method for the preparation of a protein by yeasts. In particular, the method of the invention concerns transforming a yeast cell with a first DNA fragment encoding the protein and a second DNA fragment that encodes the receptor. The method further entails culturing the transformed yeast cell, and isolating the protein. The first DNA fragment is under control of elements providing for expression of the DNA fragment in yeast, which elements include a higher eukaryotic positive transcription control sequence consisting of a natural ligand responsive element activating sequence or a variant. The receptor is a natural nuclear receptor selected from the group consisting of receptors for steroids or for retinoids or for thyroid hormones or for vitamin D3. The receptor includes a first fragment that recognizes said ligand and a second fragment that binds to said transcriptional control sequence.

Method for the preparation of a protein by yeasts using an inducible system, vectors and correspondence transformed strains

Pharmaceutical compositions are disclosed which comprise recombinant viruses containing a DNA fragment encoding a polypeptide recognized by a particular antibody H23, which recognizes a particular tumor antigen expressed on breast cancer cells. This antibody specifically binds to an epitope comprising a tandem repeat sequence of 20 amino acids comprised in a transmembrane form as well as a secreted form of the polypeptide specifically bound by antibody H23.

Pharmaceutical composition for the treatment or prevention of a malignant tumor

Polynucleotide encoding transcriptional intermediary factor-2

The application provides a polypeptide and a pharmaceutical composition which comprises said polypeptide, wherein said polypeptide is recognized by a particular antibody H23, which recognizes a particular tumor antigen expressed on breast cancer cells. This antibody specifically binds to an epitope comprising a tandem repeat sequence of 20 amino acids comprised in a transmembrane form as well as a secreted form of the polypeptides specifically bound by antibody H23.

The present invention provides compositions and methods for treating an animal, preferably a human, suffering from or predisposed to a physical disorder by administering an effective amount of a composition comprising at least one RAR antagonist, preferably an RAR.alpha. antagonist, and at least one RXR agonist. The combination of an RXR agonist, which has no therapeutic effects alone, with an RAR antagonist allows the use of lower doses of the RAR antagonist than were previously thought to be efficacious; this approach obviates many of the undesirable physiological side-effects of treatment with RAR antagonists.

Therapeutic combinations of RAR antagonists and RXR agonists and use

Growing community of inventors

Blaesheim, France

Pierre H Chambon