NUCLEIC ACIDS FOR RELEASING THE TUMOR CELL NUMBER OF DEATHS

USE OF A COMBINATION OF DBAIT MOLECULE AND PARP INHIBITORS TO TREAT CANCER

The present invention relates to the combination of a PARP inhibitor with a Dbait molecule for treating cancer.

Optimized in vivo delivery system with endosomolytic agents for nucleic acid conjugates

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

DBAIT AND USES THEREOF

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumor cell nuclei in order to neutralize transiently their DNA repair capacity and trigger their death.

DBAIT and uses thereof

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules. that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumor cell nuclei in order to neutralize transiently their DNA repair capacity and trigger their death.

Cancer treatment by combining DNA molecules mimicking double strand breaks with hyperthermia

The present invention relates to a method for treating a cancer including a combination of a treatment by a nucleic acid molecule mimicking double strand breaks with hyperthermia.

Dbait and uses thereof

Optimized in vivo delivery system with endosomolytic agents for nucleic acid conjugates

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

DBAIT AND USES THEREOF

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumor cell nuclei in order to neutralize transiently their DNA repair capacity and trigger their death.

CANCER TREATMENT BY COMBINING DNA MOLECULES MIMICKING DOUBLE STRAND BREAKS WITH HYPERTHERMIA

The present invention relates to a method for treating a cancer including a combination of a treatment by a nucleic acid molecule mimicking double strand breaks with hyperthermia.

TREATMENT OF CANCER BY SYSTEMIC ADMINISTRATION OF DBAIT MOLECULES

The present invention relates to the use of a DBait molecules by systemic routes without any combination with an endosomolytic agent.

IRREVERSIBLE COLLOIDAL CHAINS WITH RECOGNITION SITES

Methods and compositions for effecting homologous recombination

OPTIMIZED IN VIVO DELIVERY SYSTEM WITH ENDOSOMOLYTIC AGENTS FOR NUCLEIC ACID CONJUGATES

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

Assembly of colloidal particles in the form of irreversibly organized chains bearing species-recognition sites, e.g. useful for chromatography or electrophoresis, as a microreactor or in combinatorial chemistry

La présente invention a pour objet principal un assemblage de particules colloïdales sous la forme d'une ou plusieurs chaînes caractérisé en ce que lesdites chaînes sont organisées de manière irréversible et sont porteuses d'au moins un site de reconnaissance pour une espèce, ledit site étant différent des sites impliqués dans l'organisation linéaire desdites particules. Elle vise également un procédé de préparation d'un tel assemblage et l'utilisation de cet assemblage, notamment à des fins de détection et/ou de dosage d'au moins une espèce dans un fluide. L'invention concerne également un élément de surface fonctionnalisé à l'aide d'un assemblage de chaînes colloïdales et un réseau d'hybridation comportant un tel élément de surface.

USE OF A COMBINATION OF DBAIT MOLECULE AND PARP INHIBITORS TO TREAT CANCER

The present invention relates to the combination of a PARP inhibitor with a Dbait molecule for treating cancer.

DBAIT AND ITS STANDALONE USES THEREOF

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as a standalone anticancer drug in an efficient amount to be introduced in the tumor cell nuclei in order to trigger their death.

Optimized in vivo delivery system with endosomolytic agents for nucleic acid conjugates

The present invention relates to the pharmaceutical field, and concretely relates to the field of oncology. The invention discloses an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

OPTIMIZED IN VIVO DELIVERY SYSTEM WITH ENDOSOMOLYTIC AGENTS FOR NUCLEIC ACID CONJUGATES

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer. 2. The conjugated nucleic acid molecule according to claim 1 , wherein n is 27.3. The conjugated nucleic acid molecule according to claim 1 , wherein C is selected from the group consisting of tocopherol and cholesterol.4. The conjugated nucleic acid molecule according to claim 1 , wherein L′ is a loop linking the two strands of the nucleic acid molecule.5. The conjugated nucleic acid molecule according to claim 1 , wherein L′ is selected from the group consisting of a nucleotide linker and a non-nucleotide linker.6. The conjugated nucleic acid molecule according to claim 5 , wherein L′ is a non-nucleotide linker selected from the group consisting of abasic nucleotide claim 5 , polyether claim 5 , polyamine claim 5 , polyamide claim 5 , peptide claim 5 , carbohydrate claim 5 , lipid claim 5 , polyhydrocarbon and polymeric compounds.7. The conjugated nucleic acid molecule according to claim 5 , wherein L′ is selected from the group consisting of hexaethyleneglycol claim 5 , tetradeoxythymidylate (T4) claim 5 , 1 claim 5 ,19-bis(phospho)-8-hydraza-2-hydroxy-4-oxa-9-oxo-nonadecane and 2 claim 5 ,19-bis(phosphor)-8-hydraza-1-hydroxy-4-oxa-9-oxo-nonadecane.8. The conjugated nucleic acid molecule according to claim 1 , wherein L is selected from the group consisting of aliphatic chain claim 1 , polyether claim 1 , polyamine claim 1 , polyamide claim 1 , peptide claim 1 , carbohydrate claim 1 , lipid claim 1 , polyhydrocarbon claim 1 , polymeric compounds and compounds incorporating a disulfide linkage claim 1 , a protected disulfide linkage claim 1 , an amide linkage claim 1 , an acid labile linkage claim 1 , an ester linkage claim 1 , an ortho ester linkage claim 1 , a phosphonamide linkage claim 1 , a biocleavable peptide linkage claim 1 ...

Optimized in vivo delivery system with endosomolytic agents for nucleic acid conjugates

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

Use of a combination of Dbait molecule and parp inhibitors to treat cancer

The present invention relates to the combination of a PARP inhibitor with a Dbait molecule for treating cancer.

DBAIT AND ITS STANDALONE USES THEREOF

The invention relates to compositions and methods for interfering with th e DNA repair of double strand breaks (DSBs). The invention discloses double- stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways , in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as a standalone anticanc er drug in an efficient amount to be introduced in the tumor cell nuclei in order to trigger their death.

OPTIMIZED IN VIVO DELIVERY SYSTEM WITH ENDOSOMOLYTIC AGENTS FOR NUCLEIC ACID CONJUGATES

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

Optimized in vivo delivery system with endosomolytic agents for nucleic acid conjugates

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

Cancer treatment by combining DNA molecules mimicking double strand breaks with hyperthermia

The present invention relates to a method for treating a cancer including a combination of a treatment by a nucleic acid molecule mimicking double strand breaks with hyperthermia.

Use of a combination of Dbait molecule and parp inhibitors to treat cancer

The present invention relates to the combination of a PARP inhibitor with a Dbait molecule for treating cancer.

A DBAIT MOLECULE AGAINST ACQUIRED RESISTANCE IN THE TREATMENT OF CANCER

The invention relates to a method for delaying and/or preventing development of cancer resistant to a cancer therapy agent in a patient based on administration of a Dbait molecule.

IRREVERSIBLE COLLOIDAL CHAINS CARRYING SITES OF RECOGNITION, LEURPROCEDE OF PREPARATION AND APPLICATION HAS ENDS OF DETECTION Of SPECIES

Dbait and standalone uses thereof

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible for DNA DSB sensing, signaling and/or repair pathways, in particular the non-homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as a standalone anticancer drug in an efficient amount to be introduced in the tumor cell nuclei in order to trigger their death.

Dbait and its standalone uses thereof

Dbait and its standalone uses thereof

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as a standalone anticancer drug in an efficient amount to be introduced in the tumor cell nuclei in order to trigger their death.

Nucleic acids useful for triggering tumor cell lethality

A Dbait molecule against acquired resistance in the treatment of cancer

The invention relates to a method for delaying and/or preventing development of cancer resistant to a cancer therapy agent in a patient based on administration of a Dbait molecule.

Dbait and uses thereof

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumor cell nuclei in order to neutralize transiently their DNA repair capacity and trigger their death.

Dbait and its standalone uses thereof

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as a standalone anticancer drug in an efficient amount to be introduced in the tumor cell nuclei in order to trigger their death.

Optimized in vivo delivery system with endosomolytic agents for nucleic acid conjugates

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

Optimized in vivo delivery system with endosomolytic agents for nucleic acid conjugates

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

Optimized in vivo delivery system with endosomolytic agents for nucleic acid conjugates

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

Nucleic acids useful for triggering tumor cell lethality

The invention relate to double stranded nucleic acid fragments comprising a chemically modified backbone and at least 4-1000 bp, preferably 8-500 bp, and most preferably 12-100 bp.Application as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumoral cell nuclei in order to trigger DNA repair induced lethality (DRIL in short) of tumoral cells / tissues.

NUKLEINSÄUREN ZUM AUSLÖSEN DER TUMORZELLSTERBLICHKEIT

Nucleic acids useful for triggering tumor cell lethality

The invention relates to double-stranded nucleic acid fragments comprising a chemically modified backbone and at least 4-1000 bp, preferably 8-500 bp, and most preferably 16-200 bp. The disclosed molecules (DRIL molecules) may interfere with DNA damage signaling and repair pathways, in particular the non homologous NHEJ pathway of double-stranded break repair. The invention discloses the application of the DRIL molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumoral cell nuclei in order to trigger DNA repair induced lethality (DRIL in short) of tumoral cells/tissues.

TREATMENT OF CANCER BY SYSTEMIC ADMINISTRATION OF DBAIT MOLECULES

The present invention relates to the use of a DBait molecules by systemic routes without any combination with an endosomolytic agent.

DBAIT AND USES THEREOF

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules. that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumor cell nuclei in order to neutralize transiently their DNA repair capacity and trigger their death.

Dbait and its standalone uses thereof

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as a standalone anticancer drug in an efficient amount to be introduced in the tumor cell nuclei in order to trigger their death.

Irreversible colloidal chanis with recognition sites

A collection of colloidal particles in the form of one or several chains, in which the chains are generated in an irreversible manner and have at least one recognition site for a species, the site being different from sites implicated in the linear organisation of the particles. The invention further relates to a method for production of the collection, particularly for detection and/or dosage of at least one species in a fluid and a surface element functionalised by a collection of colloidal chains and a hybridisation network including such a surface element.

Methods and compositions for effecting homologous recombination

This invention concerns a method for effecting directed mutagenesis based on a guided homologous recombination system that comprises (i) a triple helix forming oligonucleotide, (ii) a donor nucleic acid segment, and (iii) an adapter segment comprising an oligonucleotide sequence able to bind at least a portion of said donor nucleic acid through Watson-Crick base pairing.

NUCLEIC ACID USEFUL FOR TRIGGERING TUMOR CELL LETHALITY

【課題】抗がん性治療を受けた腫瘍の細胞致死性をトリガーするためのツールとして有用な核酸の提供。 【解決手段】２４〜１００bpの二本鎖部分を含み、少なくとも１つの自由端を有し、そして二本鎖切断修復のＮＨＥＪ経路に関与する少なくともＫｕタンパク質により結合するための基質である核酸分子。好ましくは、ＤＮＡ断片からなる線状又はヘアピン核酸分子であり、そのループが、リンカー、ヘキサエチレングリコール又はテトラデオキシチミジレートである。当該二本鎖核酸断片は、ＤＮＡ損傷シグナリング及び修復経路、特に二本鎖切断修復の非相同性ＮＨＥＪ経路を妨害することができ、ＤＮＡ切断処置、特に放射線治療又は化学療法と共同して使用されるべき佐剤組成物として使用される。 【選択図】なし

Dbait and uses thereof

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumor cell nuclei in order to neutralize transiently their DNA repair capacity and trigger their death.

Dbait and its Standalone Uses Thereof

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non-homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as a standalone anticancer drug in an efficient amount to be introduced in the tumor cell nuclei in order to trigger their death.

Optimized in vivo delivery system with endosomolytic agents for nucleic acid conjugates

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

Dbait and uses thereof

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules. that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumor cell nuclei in order to neutralize transiently their DNA repair capacity and trigger their death.

Cancer treatment by combining DNA molecules mimicking double strand breaks with hyperthermia

The present invention relates to a method for treating a cancer including a combination of a treatment by a nucleic acid molecule mimicking double strand breaks with hyperthermia.

NUCLEIC ACIDS USEFUL FOR TRIGGERING TUMOR CELL LETHALITY

Use of a combination of Dbait molecule and PARP inhibitors to treat cancer

The present invention relates to the combination of a PARP inhibitor with a Dbait molecule for treating cancer.

A DBAIT MOLECULE AGAINST ACQUIRED RESISTANCE IN THE TREATMENT OF CANCER

The invention relates to a method for delaying and/or preventing development of cancer resistant to a cancer therapy agent in a patient based on administration of a Dbait molecule.

Use of a combination of Dbait molecule and PARP inhibitors to treat cancer

The present invention relates to the combination of a PARP inhibitor with a Dbait molecule for treating cancer.

OPTIMIZED IN VIVO DELIVERY SYSTEM WITH ENDOSOMOLYTIC AGENTS FOR NUCLEIC ACID CONJUGATES

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer. 2. The conjugated nucleic acid molecule according to claim 1 , wherein n is 27.3. The conjugated nucleic acid molecule according to claim 1 , wherein C is selected from the group consisting of tocopherol and cholesterol.4. The conjugated nucleic acid molecule according to claim 1 , wherein L′ is a loop linking the two strands of the nucleic acid molecule.5. The conjugated nucleic acid molecule according to claim 1 , wherein L′ is selected from the group consisting of a nucleotide linker and a non-nucleotide linker.6. The conjugated nucleic acid molecule according to claim 5 , wherein L′ is a non-nucleotide linker selected from the group consisting of abasic nucleotide claim 5 , polyether claim 5 , polyamine claim 5 , polyamide claim 5 , peptide claim 5 , carbohydrate claim 5 , lipid claim 5 , polyhydrocarbon and polymeric compounds.7. The conjugated nucleic acid molecule according to claim 5 , wherein L′ is selected from the group consisting of hexaethyleneglycol claim 5 , tetradeoxythymidylate (T4) claim 5 , 1 claim 5 ,19-bis(phospho)-8-hydraza-2-hydroxy-4-oxa-9-oxo-nonadecane and 2 claim 5 ,19-bis(phosphor)-8-hydraza-1-hydroxy-4-oxa-9-oxo-nonadecane.8. The conjugated nucleic acid molecule according to claim 1 , wherein L is selected from the group consisting of aliphatic chain claim 1 , polyether claim 1 , polyamine claim 1 , polyamide claim 1 , peptide claim 1 , carbohydrate claim 1 , lipid claim 1 , polyhydrocarbon claim 1 , polymeric compounds and compounds incorporating a disulfide linkage claim 1 , a protected disulfide linkage claim 1 , an amide linkage claim 1 , an acid labile linkage claim 1 , an ester linkage claim 1 , an ortho ester linkage claim 1 , a phosphonamide linkage claim 1 , a biocleavable peptide linkage claim 1 ...

OPTIMIZED IN VIVO DELIVERY SYSTEM WITH ENDOSOMOLYTIC AGENTS FOR NUCLEIC ACID CONJUGATES

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer. 2. The conjugated nucleic acid molecule of claim 1 , wherein n is 27.3. The conjugated nucleic acid molecule according to claim 1 , wherein the molecule facilitating endocytosis is selected from the group consisting of tocopherol and cholesterol.4. The conjugated nucleic acid molecule according to claim 2 , wherein the molecule facilitating endocytosis is selected from the group consisting of tocopherol and cholesterol.6. A pharmaceutical composition comprising a conjugated nucleic acid molecule according to .7. The pharmaceutical composition of claim 6 , wherein said composition further comprises a DNA-damaging anti-tumoral agent and a pharmaceutically acceptable carrier.8. A pharmaceutical composition comprising a conjugated nucleic acid molecule according to .9. The pharmaceutical composition of claim 8 , wherein said composition further comprises a DNA-damaging anti-tumoral agent and a pharmaceutically acceptable carrier.10. A pharmaceutical composition comprising a conjugated nucleic acid molecule according to .11. The pharmaceutical composition of claim 10 , wherein said composition further comprises a DNA-damaging anti-tumoral agent and a pharmaceutically acceptable carrier.12. A kit comprising a conjugated nucleic acid molecule according to and a DNA-damaging anti-tumoral agent claim 1 , as a combined preparation for simultaneous claim 1 , separate or sequential use.13. A kit comprising a conjugated nucleic acid molecule according to and a DNA-damaging anti-tumoral agent claim 2 , as a combined preparation for simultaneous claim 2 , separate or sequential use.14. A kit comprising a conjugated nucleic acid molecule according to and a DNA-damaging anti-tumoral agent claim 3 , as a combined preparation for simultaneous claim 3 , ...

Treatment of cancer by systemic administration of Dbait molecules

The present invention relates to the use of a DBait molecules by systemic routes without any combination with an endosomolytic agent.

Nucleic acid useful for triggering tumor cell lethality

The invention relates to double-stranded nucleic acid fragments comprising a chemically modified backbone and at least 4-1000 bp, preferably 8-500 bp, and most preferably 16-200 bp. The disclosed molecules (DRIL molecules) may interfere with DNA damage signalling and repair pathways, in particular the non homologous NHEJ pathway of double-stranded break repair. The invention discloses the application of the DRIL molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumoral cell nuclei in order to trigger DNA repair induced lethality (DRIL in short) of tumoral cells/tissues.

TREATMENT OF CANCER BY SYSTEMIC ADMINISTRATION OF DBAIT MOLECULES

The present invention relates to the use of a DBait molecules by systemic routes without any combination with an endosomolytic agent. 2. The method according to claim 1 , wherein the nucleic acid of formula (I) has one or several of the following features:N is a deoxynucleotide selected from the group consisting of A (adenine), C (cytosine), T (thymine) and G (guanine) and selected so as to avoid occurrence of a CpG dinucleotide and to have less than 80% sequence identity to any gene in a human genome; and/orthe linked L′ is selected from the group consisting of hexaethyleneglycol, tetradeoxythymidylate (T4) and 1,19-bis(phospho)-8-hydraza-2-hydroxy-4-oxa-9-oxo-nonadecane; and/orm is 1 and L is a carboxamido polyethylene glycol; and/orC is selected from the group consisting of a cholesterol, single or double chain fatty acids and a ligand which targets cell receptor.5. The method according to claim 1 , wherein the nucleic acid is to be administered by intravenous route.6. The method according to claim 5 , wherein the nucleic acid is to be administered by injection claim 5 , intravenous drip claim 5 , bolus or pump.7. The method according to claim 1 , wherein the nucleic acid is administered in combination with antitumor treatment.8. The method according to claim 1 , wherein the nucleic acid is administered in combination with radiotherapy and/or chemotherapy.9. The method according to claim 1 , wherein the nucleic acid is administered in combination with a DNA damaging anti-tumor agent.10. The method according to claim 9 , wherein the DNA damaging anti-tumor agent is selected from the group consisting of an inhibitor of topoisomerases I or II claim 9 , a DNA crosslinker claim 9 , a DNA alkylating agent claim 9 , an anti-metabolic agent and inhibitors of the mitotic spindles.11. The method according to claim 1 , wherein the nucleic acid is to be used in combination with a platinum drug selected from the group consisting of oxaliplatin claim 1 , carboplatin and ...

Dbait and uses thereof

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumor cell nuclei in order to neutralize transiently their DNA repair capacity and trigger their death.

USE OF A COMBINATION OF DBAIT MOLECULE AND PARP INHIBITORS TO TREAT CANCER

The present invention relates to the combination of a PARP inhibitor with a Dbait molecule for treating cancer. 2. A method of treating cancer comprising the administration of a pharmaceutical composition according to to a subject having cancer.4. The pharmaceutical composition according to claim 1 , wherein the molecule of formula (I) claim 1 , (II) or (III) has one or several of the following features:n is an integer from 23 to 195 or from 27 to 95; and/orN is a deoxynucleotide selected from the group consisting of A (adenine), C (cytosine), T (thymine) and G (guanine) and selected so as to avoid occurrence of a CpG dinucleotide and to have less than 80% sequence identity to any gene in a human genome; and/orthe linked L′ is selected from the group consisting of hexaethyleneglycol, tetradeoxythymidylate (T4), 1,19-bis(phospho)-8-hydraza-2-hydroxy-4-oxa-9-oxo-nonadecane and 2,19-bis(phosphor)-8-hydraza-1-hydroxy-4-oxa-9-oxo-nonadecane; and/orm is 1 and L is a carboxamido polyethylene glycol, more preferably carboxamido triethylene glycol or carboxamido tetraethylene glycol; and/orC is selected from the group consisting of a cholesterol, single or double chain fatty acids such as octadecyl, oleic acid, dioleoyl or stearic acid, or ligand (including peptide, protein, aptamer) which targets cell receptor such as folic acid, tocopherol, sugar such as galactose and mannose and their oligosaccharide, peptide such as RGD and bombesin, and protein such transferring and integrin, preferably is a cholesterol or a tocopherol, still more preferably a cholesterol.9. The pharmaceutical composition according to claim 1 , wherein the PARP inhibitor is selected from the group consisting of rucaparib (AG014699 claim 1 , PF-01367338) claim 1 , olaparib (AZD2281) claim 1 , veliparib (ABT888) claim 1 , iniparib (BSI 201) claim 1 , niraparib (MK 4827) claim 1 , talazoparib (BMN673) claim 1 , AZD 2461 claim 1 , CEP 9722 claim 1 , E7016 claim 1 , INO-1001 claim 1 , LT-673 claim 1 , MP-124 ...

Optimized in vivo delivery system with endosomolytic agents for nucleic acid conjugates

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

USE OF A COMBINATION OF DBAIT MOLECULE AND PARP INHIBITORS TO TREAT CANCER

The present invention relates to the combination of a PARP inhibitor with a Dbait molecule for treating cancer.

CANCER TREATMENT BY COMBINING DNA MOLECULES MIMICKING DOUBLE STRAND BREAKS WITH HYPERTHERMIA

The present invention relates to a method for treating a cancer including a combination of a treatment by a nucleic acid molecule mimicking double strand breaks with hyperthermia.

Cancer treatment by combining dna molecules mimicking double strand breaks with hyperthermia

The present invention relates to a method for treating a cancer including a combination of a treatment by a nucleic acid molecule mimicking double strand breaks with hyperthermia.

Dbait and uses thereof

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumor cell nuclei in order to neutralize transiently their DNA repair capacity and trigger their death.

Optimized In Vivo Delivery System with Endosomolytic Agents for Nucleic Acid Conjugates

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer. 114-. (canceled)15. A pharmaceutical composition comprising:a) a conjugated nucleic acid molecule having at least one free end and a DNA double stranded portion of 20-200 bp with less than 80% sequence identity to any gene in a human genome, said nucleic acid molecule being covalently linked to a molecule facilitating endocytosis selected from a lipophilic molecule or a ligand which targets cell receptor enabling receptor mediated endocytosis, andb) a quinoline endomosolytic agent.16. The composition of claim 15 , wherein the composition further comprises a DNA damaging antitumoral agent.17. The composition of claim 15 , wherein the quinoline endomosolytic agent is chloroquine or hydroxychloroquine.18. The composition of claim 15 , wherein the molecule facilitating endocytosis is selected from the group consisting of single or double chain fatty acids claim 15 , cholesterol claim 15 , sugars claim 15 , peptides claim 15 , and proteins.19. The composition of claim 18 , wherein the molecule facilitating endocytosis is octodecyl claim 18 , dioleoyl claim 18 , tocopherol claim 18 , folate claim 18 , folic acid claim 18 , galactose claim 18 , mannose claim 18 , oligosaccharides claim 18 , RGD peptides claim 18 , bombesin or an integrin.22. The composition of claim 15 , wherein the molecule facilitating endocytosis is cholesterol.24. A product comprising:a) a conjugated nucleic acid molecule having at least one free end and a DNA double stranded portion of 20-200 bp with less than 80% sequence identity to any gene in a human genome, said nucleic acid molecule being covalently linked to a molecule facilitating endocytosis selected from a lipophilic molecule or a ligand which targets cell receptor enabling receptor mediated endocytosis, andb ...

OPTIMIZED IN VIVO DELIVERY SYSTEM WITH ENDOSOMOLYTIC AGENTS FOR NUCLEIC ACID CONJUGATES

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer. 2. The conjugated nucleic acid molecule according to claim 1 , wherein the molecule facilitating endocytosis is selected from the group consisting of tocopherol and cholesterol.4. A pharmaceutical composition comprising a conjugated nucleic acid molecule according to .5. A pharmaceutical composition comprising a conjugated nucleic acid molecule according to .6. The pharmaceutical composition of claim 5 , wherein it further comprises a DNA-damaging anti-tumoral agent and a pharmaceutically acceptable carrier.7. A kit comprising a conjugated nucleic acid molecule according to and a DNA-damaging anti-tumoral agent claim 3 , as a combined preparation for simultaneous claim 3 , separate or sequential use.8. The pharmaceutical composition of claim 4 , wherein it further comprises a DNA-damaging anti-tumoral agent and a pharmaceutically acceptable carrier.9. A kit comprising a conjugated nucleic acid molecule according to and a DNA-damaging anti-tumoral agent claim 1 , as a combined preparation for simultaneous claim 1 , separate or sequential use.10. A method for treating a cancer in a subject in need thereof claim 1 , comprising administering an effective amount of conjugated nucleic acid molecule of .11. A method for treating a cancer in a subject in need thereof claim 3 , comprising administering an effective amount of conjugated nucleic acid molecule of .12. The method of claim 10 , wherein the treatment further comprises radiotherapy or chemotherapy claim 10 , optionally with a DNA damaging antitumoral agent.13. The method of claim 11 , wherein the treatment further comprises radiotherapy or chemotherapy claim 11 , optionally with a DNA damaging antitumoral agent. This application is a continuation of U.S. application Ser. No. 13/703, ...

TREATMENT OF CANCER BY SYSTEMIC ADMINISTRATION OF DBAIT MOLECULES

The present invention relates to the use of a DBait molecules by systemic routes without any combination with an endosomolytic agent. 113-. (canceled)15. The method according to claim 14 , wherein the nucleic acid of formula (I) has one or several of the following features:N is a deoxynucleotide selected from the group consisting of A (adenine), C (cytosine), T (thymine) and G (guanine) and selected so as to avoid occurrence of a CpG dinucleotide and to have less than 80% sequence identity to any gene in a human genome; and/orthe linked L′ is selected from the group consisting of hexaethyleneglycol, tetradeoxythymidylate (T4) and 1,19-bis(phospho)-8-hydraza-2-hydroxy-4-oxa-9-oxo-nonadecane; and/orm is 1 and L is a carboxamido polyethylene glycol; and/orC is selected from the group consisting of a cholesterol, single or double chain fatty acids and a ligand which targets cell receptor.18. The method according to claim 14 , wherein the nucleic acid is to be administered by intravenous route.19. The method according to claim 18 , wherein the nucleic acid is to be administered by injection claim 18 , intravenous drip claim 18 , bolus or pump.20. The method according to claim 14 , wherein the cancer is a chemoresistant cancer.21. The method according to claim 20 , wherein the chemoresistant cancer is selected from the group consisting of a triple-negative breast cancer (TNBC) claim 20 , a chemoresistant lung cancer and a chemoresistant ovarian cancer.22. The method according to claim 21 , wherein the chemoresistant cancer is a platinum-resistant cancer.23. The method according to claim 22 , wherein the platinum-resistant cancer is selected from the group consisting of a platinum-resistant ovarian cancer and a platinum-resistant triple-negative breast cancer.24. The method according to claim 14 , wherein the nucleic acid is administered in combination with radiotherapy and/or chemotherapy.25. The method according to claim 14 , wherein the nucleic acid is administered in ...

A dbait molecule against acquired resistance in the treatment of cancer

The invention relates to a method for delaying and/or preventing development of cancer resistant to a cancer therapy agent in a patient based on administration of a Dbait molecule.

Dbait and uses thereof

Dbait ir jų panaudojimas

New predictive biomarker for the sensitivity to a treatment of cancer with a dbait molecule

The present invention relates to a biomarker which is predictive of the sensitivity to a treatment of cancer with a Dbait molecule.

Use of a combination of dbait molecule and parp inhibitors to treat cancer

The present invention relates to the combination of a PARP inhibitor with a Dbait molecule for treating cancer.

Methods and compositions for effecting homologous recombination

This invention concerns a method for effecting homologous recombination between a native nucleic acid segment in a cell and a donor nucleic acid segment introduced into the cell, which comprises: a) introducing into a cel l a nucleic acid delivery system comprising: (i) an oligonucleotide third stra nd which comprises a base sequence capable of forming a triple helix at a bindi ng region on one or both strands of a native nucleic acid segment, (ii) a donor nucleic acid, comprising a nucleic acid sequence sufficiently homologous to the native nucleic acid segment such that the donor sequence is capable of undergoing homologous recombination with the native sequence at the target region, (iii) an adapter segment comprising an oligonucleotide sequence able to bind at least a portion of said donor nucleic acid through Watson-Crick base pairing, the adapter segment being linked to said oligonucleotide third strand, b) allowing the oligonucleotide to bind to the native nucleic acid segment to form a triple helix nucleic acid, thereby inducing homologous recombination at the native nucleic acid segment target region; and c) allowing homologous recombination to occur between the native and donor nucleic acid segments. The method may namely be implemented for effecting ge ne alteration or mutation repair at a specific sequence site on a native DNA.</ SDOAB>

Dbait and its standalone uses thereof

The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses double-stranded nucleic acid molecules that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as a standalone anticancer drug in an efficient amount to be introduced in the tumor cell nuclei in order to trigger their death.

Irreversible colloidal chains with recognition sites

The invention relates to a collection of colloidal particles in the form of one or several chains, characterised in that said chains are generated in an irreversible manner and have at least one recognition site for a species, said site being different from sites implicated in the linear organisation of said particles. The invention further relates to a method for production of said collection, particularly for detection and/or dosage of at least one species in a fluid and a surface element functionalised by means of a collection of colloidal chains and a hybridisation network comprising such a surface element.

Irreversible colloidal chains with recognition sites

The invention relates to a collection of colloidal particles in the form of one or several chains, characterised in that said chains are generated in an irreversible manner and have at least one recognition site for a species, said site being different from sites implicated in the linear organisation of said particles. The invention further relates to a method for production of said collection, particularly for detection and/or dosage of at least one species in a fluid and a surface element functionalised by means of a collection of colloidal chains and a hybridisation network comprising such a surface element.

USING A COMBINATION OF DBAIT MOLECULES AND PARP INHIBITORS FOR TREATMENT OF CANCER

Use of a combination of dbait molecule and parp inhibitors to treat cancer

Optimized in vivo delivery system with endosomolytic agents for nucleic acid conjugates

A method of predicting a response to an anti-tumor treatment by means of signal interfering dna molecules

The present invention relates to a method of predicting a response to an anti-tumor treatment, more particularly to the identification of a marker for predicting whether a nucleic acid molecule able to inhibit DNA repair (Dbait molecule) would be effective for treating a tumor in a patient.

Νουκλεϊκα οξεα χρησιμα για την πυροδοτηση της θνησιμοτητας κυτταρων ογκου

Η εφεύρεση αφορά θραύσματα δίκλωνου νουκλεϊκού οξέος, τα οποία περιλαμβάνουν μια χημικά τροποποιημένη ραχοκοκκαλιά τουλάχιστον 4-1000bp, κατά προτίμηση 8-500 bp, και κατά μεγίστη προτίμηση 16-200 bp. Τα αποκαλυπτόμενα μόρια (μόρια DRIL) μπορούν να παρέμβουν σε σηματοδότηση βλάβης DNA και μονοπάτια αποκατάστασης, ειδικότερα το μη ομόλογο μονοπάτι NHEJ αποκατάστασης θραύσης διπλής έλικας. Η εφεύρεση αποκαλύπτει την εφαρμογή των μορίων DRIL ως βοηθητικές συνθέσεις προς χρήση σε συνδυασμό με μια αγωγή θραύσης DNA, ειδικότερα ραδιοθεραπεία ή χημειοθεραπεία, σε συνδυασμό με ένα φαρμακευτικά αποδεκτό φορέα, σε μια αποτελεσματική ποσότητα, η οποία εισάγεται εις τους πυρήνες των κυττάρων του όγκου προκειμένου να πυροδοτήσει την θνησιμότητα (εν συντομία DRIL) των κυττάρων / ιστών του όγκου, η οποία προκαλείται δια αποκατάστασης DNA.

Nukleinske kisline uporabne za sproĺ˝anje letalnosti tumorske celice

Nucleic acids useful for triggering tumor cell lethality

The invention relates to double-stranded nucleic acid fragments comprising a chemically modified backdone and at least 4-1000 bp, preferably 8-500 bp, and most preferably 16-200 bp. The disclosed molecules (DRIL molecules) may interfere with DNA damage signalling and repair pathways, in particular the non homologous NHEJ pathway of double-stranded break repair. The invention discloses the application of the DRIL molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumoral cell nuclei in order to trigger DNA repair induced lethality (DRIL in short) of tumoral cells/tissues.

Nucleic acids useful for triggering tumor cell lethality

The invention relate to double stranded nucleic acid fragments comprising a chemically modified backbone and at least 4-1000 bp, preferably 8-500 bp, and most preferably 12-100 bp.Application as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumoral cell nuclei in order to trigger DNA repair induced lethality (DRIL in short) of tumoral cells / tissues.

Kwasy nukleinowe użyteczne do wywoływania śmiertelności komórek nowotworowych

Ácidos nucleicos útiles para desencadenar la mortalidad de células tumorales.

- Uso de una molécula de ácido nucleico que comprende una parte de doble cadena de 24- 100 bp, que tiene al menos un extremo libre y que es sustrato de unión por al menos una proteína Ku involucrada en la vía NHEJ de reparación de roturas de dobles cadenas, para fabricar un medicamento para intensificar la sensibilidad tumoral a terapia anticancerosa que daña el DNA.

Nukleinsäuren zum auslösen der tumorzellsterblichkeit