Sanofi

Aventis Pharma S.a.

Roussel Uclaf

Université Clermont Auvergne

Sanifi

Sanofi Mature IP

Bruno Dumas

Roberto Spagnoli

Denis Pompon

Eric Degryse

Tilman Achstetter

Gilles Cauet

Nabil Lounis

Isabelle Bonnin

Marine Bertin

Jacques Winter

Corinne Brocard-Masson

Monica Gervais

Catherine Devaud

Elisabeth Billard

Mathilde Bonnet

Amélie Lopes

Francoise X Jousset

Mireille Jourdan

Max Bergoin

A method of predicting resistance to anti-PD1 therapy in a subject suffering from cancer comprising the steps of a) determining, from a biological sample from a subject, in particular a feces or colonic biopsy sample from the subject, the presence of a bacterial pks island, b) predicting from the result of step a) that the subject is likely to be resistant to anti-PD1 therapy, is provided. Methods of treating cancer in a subject by assessing the presence or absence of bacterial pks island in a biological sample from a subject, in particular a feces or colonic biopsy sample from the subject and administering to the subject an anti-cancer therapy are also provided.

PKS-island positiveas marker of negative response to anti-PD1 therapy in colorectal cancer

The present invention is within the field of industrial protein production. The invention provides a novel expression system using dehydroorotate dehydrogenase (DHODH) as a selection marker in combination with leflunomide or a metabolite thereof, notably for use in mammalian cell lines. Expression vectors encoding DHODH, cell lines comprising said vectors and methods of producing recombinant proteins are also provided.

Selection marker for cell transfection and protein production

The present invention is within the field of industrial protein production. The invention provides a novel expression system using dihydroorotate dehydrogenase (DHODH) as a selection marker in combination with leflunomide or a metabolite thereof, notably for use in mammalian cell lines. Expression vectors encoding DHODH, cell lines comprising said vectors and methods of producing recombinant proteins are also provided.

The subject of the present invention is a process for preparing a genetically modified yeast by multicopy integration of at least four expression cassettes, allowing the production of a molecule of interest at high titer. The subject of the present invention is also yeasts transformed according to said process, and the use thereof for producing hydrocortisone.

Genetically transformed yeasts capable of producing a molecule of interest at a high titre

The present invention pertains to an isolated P450 enzyme comprising or consisting of an amino acid sequence at least 80% identical to SEQ ID NO: 1, wherein said sequence comprises a threonine at position corresponding to position 225 and/or an aspartic acid mutation at position corresponding to position 289. The invention also concerns an isolated nucleic acid comprising a sequence encoding said enzyme, a vector comprising said nucleic acid, and a host cell containing said nucleic acid or said vector. Methods for preparing said enzyme and methods for producing steroid hormone precursors using the enzyme or the host cells featured in the invention are also provided.

Cytochrome P450 polypeptide with increased enzyme activity

Process for preparing genetically transformed yeasts capable of producing a molecule of interest at a high titre

The present invention is within the field of industrial protein production. The inventors have designed and constructed a new expression system comprising an expression vector coding for a glutamine synthetase of human or dog origin, and a CHO cell line. More specifically, the invention pertains to a combination of (i) a DNA vector suitable for production of a recombinant protein, wherein said vector comprises a sequence coding for a glutamine synthetase, and (ii) a Chinese Hamster Ovary (CHO) cell line, wherein said GS comprises a sequence at least 94.5% identical to the sequence of SEQ ID NO: 1 or to the sequence of SEQ ID NO: 2.

CHO expression system

The invention concerns the production of cholesterol of the Fungi kingdom. More particularly, the invention concerns genetically modified Fungus independently producing cholesterol from a simple carbon source. The invention also concerns the use of the inventive Fungus for producing non-marked and marked cholesterol.

Desmosterol-producing yeast strains and uses thereof

The invention concerns the production of cholesterol in organisms of the Fungi kingdom. More particularly, the invention concerns genetically modified Fungus independently producing cholesterol from a simple carbon source. The invention also concerns the use of the inventive Fungus for producing non-marked and marked cholesterol.

Cholesterol-producing yeast strains and uses thereof

The present invention relates to novel yeast strains, methods and genetic constructs for their preparation, and their use for the synthesis or modification of steroidal compounds. More particularly, the invention describes strains having a reduced 20&#x3b1;HSD type activity, in particular by modifying the GCY1 and/or YPR1 genes. The yeast strains of the invention make it possible to improve the efficiency of the synthesis or to increase the selectivity or the yields of the method, as well as the quality of the final product. The strains, methods and compounds of the invention are useful in the search for, the development and the production of products with therapeutic or prophylactic activity, in humans or animals, in particular of steroidal derivatives.

Modified yeasts and uses thereof, in particular for producing steroid derivatives

The present invention relates to genetically modified yeast strains autonomously producing, from a simple carbon source, steroids. The invention also relates to a method for producing steroids from such yeast strains.

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Paris, France

Bruno Dumas