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1. 发明申请

WO2006108586A3 POLYMYXIN B ANALOGS FOR LPS DETOXIFICATION 审中-公开
标题翻译：多聚霉素B类似物用于LPS解毒
公开(公告)号：WO2006108586A3
公开(公告)日：2006-12-14
申请号：PCT/EP2006003237
申请日：2006-04-10
申请人： SANOFI PASTEUR , BIOSYNTH
发明人： PORRO MASSIMO , KRELL TINO , MISTRETTA NOELLE , MOREAU MONIQUE , RUSTICI ALESSANDRO , VELUCCHI MASSIMO
IPC分类号： C07K7/08 , A61K38/10 , A61K38/16 , C07K14/195
CPC分类号： C07K7/06 , A61K47/62
摘要： The invention relates to SAEP II peptide dimers that mimic polymyxin B i.a. in its ability to bind non-covalently the lipopolysaccharide (LPS) of Gram-negative bacteria with high affinity, and therefore to detoxify LPS as polymyxin B does. The dimeric structure is maintained by a pair of disulphide bonds involving the two cystein residues present in the peptide sequence, which does not exceed 17 amino acids and essentially comprises cationic and hydrophobic amino acid residues. In the dimers of the invention, peptides may have a parallel or anti-parallel orientation. As a matter of example, a dimer of the invention is constituted by a peptide of formula NH2-Lys-Thr-Lys-Cysl-Lys-Phe-Leu- Leu-Leu-Cys2-COOH, either in a parallel or antiparallel dimeric form. SAEP II dimers are useful for treating or preventing septic shock and related disorders generated by Gram-negative bacteria infection. The invention also relates to LPS-peptide complexes in which LPS and SAEP II dimers are non-covalently bound together. These complexes are useful as vaccinal agents against Gram-negative bacteria infection.
摘要翻译：本发明涉及模拟多粘菌素B i.a.的SAEP II肽二聚体。其能够非共价结合革兰氏阴性细菌的脂多糖（LPS）并具有高亲和力，因此可以像多粘菌素B那样将LPS解毒。二聚体结构由涉及肽序列中存在的两个半胱氨酸残基的一对二硫键维持，其不超过17个氨基酸且主要包含阳离子和疏水性氨基酸残基。在本发明的二聚体中，肽可以具有平行或反平行的取向。作为例子，本发明的二聚体由式NH 2 -Lys-Thr-Lys-Cysl-Lys-Phe-Leu-Leu-Leu-Cys 2 -COOH的肽以平行或反平行二聚体形式。 SAEP II二聚体可用于治疗或预防由革兰氏阴性菌感染产生的感染性休克和相关疾病。本发明还涉及其中LPS和SAEP II二聚体非共价结合在一起的LPS-肽复合物。这些复合物可用作抗革兰氏阴性菌感染的疫苗。

2. 发明专利

NZ561374A Polymyxin B analogs for LPS detoxification 未知
公开(公告)号：NZ561374A
公开(公告)日：2009-02-28
申请号：NZ56137406
申请日：2006-04-10
申请人： SANOFI PASTEUR , BIOSYNTH
发明人： PORRO MASSIMO , KRELL TINO , MISTRETTA NOELLE , MOREAU MONIQUE , RUSTICI ALESSANDRO , VELUCCHI MASSIMO
IPC分类号： C07K7/08 , A61K38/10 , A61K38/16 , C07K14/195
摘要： Disclosed is a SAEP II peptide dimer of formula (I) NH2-A-Cys1-B-Cys2-C-COOH NH2-A-Cys1-B-Cys2-C'-COOH wherein the two Cys1 residues are linked together through a disulphide bond and the two Cys2 residues are linked together through a disulphide bond; or formula (II) NH2-A-Cys1-B-Cys2-C-COOH HOOC-C'-Cys2-B'-,Cys1-A'-NH2 wherein the Cys1 residues are linked to the Cys2 residues through a disulphide bond ; wherein A and A' independently are a peptide moiety of from 2 to 5, amino acid residues, in which at least 2 amino acid residues, are independently selected from Lys, Hyl (hydroxy-Lysine), Arg and His; wherein B and B' independently are a peptide moiety of from 3 to 7, amino acid residues, which comprise at least two, preferably three amino acid residues independently selected from Val, Leu, Ile.Phe, Tyr andTrp ; and wherein C and C' are optional and are independently an amino acid residue or a peptide moiety of from 2 to 3 amino acid residues; provided that the cationic amino acid residues I hydrophobic amino acid residues ratio (cat/hydroph ratio) is from 0.4 to 2. Also disclosed are the use of said peptide dimer in the manufacture of medicaments and a process for producing said peptide dimer.

3. 发明专利

CA2603850A1 POLYMYXIN B ANALOGS FOR LPS DETOXIFICATION 未知
公开(公告)号：CA2603850A1
公开(公告)日：2006-10-19
申请号：CA2603850
申请日：2006-04-10
申请人： BIOSYNTH , SANOFI PASTEUR
发明人： KRELL TINO , MISTRETTA NOELLE , MOREAU MONIQUE , RUSTICI ALESSANDRO , PORRO MASSIMO , VELUCCHI MASSIMO
IPC分类号： C07K7/08 , A61K38/10 , A61K38/16 , C07K14/195
摘要： The invention relates to SAEP II peptide dimers that mimic polymyxin B i.a. in its ability to bind non-covalently the lipopolysaccharide (LPS) of Gram-negative bacteria with high affinity, and therefore to detoxify LPS as polymyxin B does. The dimeric structure is maintained by a pair of disulphide bonds involving the two cystein residues present in the peptide sequence, which does not exceed 17 amino acids and essentially comprises cationic and hydrophobic amino acid residues. In the dimers of the invention, peptides may have a parallel or anti-parallel orientation. As a matter of example, a dimer of the invention is constituted by a peptide of formula NH2-Lys-Thr-Lys-Cysl-Lys-Phe-Leu- Leu-Leu-Cys2-COOH, either in a parallel or antiparallel dimeric form. SAEP II dimers are useful for treating or preventing septic shock and related disorders generated by Gram-negative bacteria infection. The invention also relates to LPS-peptide complexes in which LPS and SAEP II dimers are non-covalently bound together. These complexes are useful as vaccinal agents against Gram-negative bacteria infection.

4. 发明专利

BRPI0610701A2 未知
公开(公告)号：BRPI0610701A2
公开(公告)日：2010-07-20
申请号：BRPI0610701
申请日：2006-04-10
申请人： BIOSYNTH , SANOFI PASTEUR
发明人： PORRO MASSIMO , KRELL TINO , MISTRETTA NOELLE , RUSTICI ALESSANDRO , VELUCCHI MASSIMO , MOREAU MONIQUE
IPC分类号： C07K7/08 , A61K38/10 , A61K38/16 , C07K14/195
摘要： The invention relates to SAEP II peptide dimers that mimic polymyxin B i.a. in its ability to bind non-covalently the lipopolysaccharide (LPS) of Gram-negative bacteria with high affinity, and therefore to detoxify LPS as polymyxin B does. The dimeric structure is maintained by a pair of disulphide bonds involving the two cystein residues present in the peptide sequence, which does not exceed 17 amino acids and essentially comprises cationic and hydrophobic amino acid residues. In the dimers of the invention, peptides may have a parallel or anti-parallel orientation. As a matter of example, a dimer of the invention is constituted by a peptide of formula NH2-Lys-Thr-Lys-Cysl-Lys-Phe-Leu- Leu-Leu-Cys2-COOH, either in a parallel or antiparallel dimeric form. SAEP II dimers are useful for treating or preventing septic shock and related disorders generated by Gram-negative bacteria infection. The invention also relates to LPS-peptide complexes in which LPS and SAEP II dimers are non-covalently bound together. These complexes are useful as vaccinal agents against Gram-negative bacteria infection.

5. 发明专利

AU2006233634A1 Polymyxin B analogs for LPS detoxification 未知
公开(公告)号：AU2006233634A1
公开(公告)日：2006-10-19
申请号：AU2006233634
申请日：2006-04-10
申请人： BIOSYNTH , SANOFI PASTEUR
发明人： KRELL TINO , PORRO MASSIMO , MISTRETTA NOELLE , VELUCCHI MASSIMO , RUSTICI ALESSANDRO , MOREAU MONIQUE
IPC分类号： A61K38/10 , A61K38/16 , C07K7/08 , C07K14/195
摘要： The invention relates to SAEP II peptide dimers that mimic polymyxin B i.a. in its ability to bind non-covalently the lipopolysaccharide (LPS) of Gram-negative bacteria with high affinity, and therefore to detoxify LPS as polymyxin B does. The dimeric structure is maintained by a pair of disulphide bonds involving the two cystein residues present in the peptide sequence, which does not exceed 17 amino acids and essentially comprises cationic and hydrophobic amino acid residues. In the dimers of the invention, peptides may have a parallel or anti-parallel orientation. As a matter of example, a dimer of the invention is constituted by a peptide of formula NH2-Lys-Thr-Lys-Cysl-Lys-Phe-Leu- Leu-Leu-Cys2-COOH, either in a parallel or antiparallel dimeric form. SAEP II dimers are useful for treating or preventing septic shock and related disorders generated by Gram-negative bacteria infection. The invention also relates to LPS-peptide complexes in which LPS and SAEP II dimers are non-covalently bound together. These complexes are useful as vaccinal agents against Gram-negative bacteria infection.

6. 发明申请

WO2010130898A3 MENIGOCOCCUS VACCINE CONTAINING LIPOOLIGOSACCHARIDE (LOS) FROM MODIFIED STRAINS OF L6 IMMUNOTYPE NEISSERIA MENINGITIDIS 审中-公开
标题翻译：含有L6寡糖的LIGOLIGOSACCHARIDE（LOS）来自L6免疫球蛋白的改良菌株
公开(公告)号：WO2010130898A3
公开(公告)日：2010-12-29
申请号：PCT/FR2010000367
申请日：2010-05-12
申请人： SANOFI PASTEUR , MISTRETTA NOELLE , MOREAU MONIQUE , RENAULD-MONGENIE GENEVIEVE , ROKBI BACHRA
发明人： MISTRETTA NOELLE , MOREAU MONIQUE , RENAULD-MONGENIE GENEVIEVE , ROKBI BACHRA
IPC分类号： C12N1/21 , A61K39/095 , C12N15/63
CPC分类号： A61K31/739 , A61K9/127 , A61K39/095
摘要： The invention particularly relates to multivalent vaccine compositions capable of treating or preventing at least 60% and preferably 75% of the infections caused by Neisseria meningitidis, in particular those of serogroup B. To this end, the invention substantially relates to lipooligosaccharide (LOS) of N. meningitidis particularly consisting of a lipid A, an inner core, and an L6 a chain, wherein the heptose II residue of the inner core has, at the O-3 position and at the O-6 or O-7 position, a phosphoethanolamine (PEA) substituent, as well as the structure of the N. meningitidis strain capable of expressing such LOS. The invention also relates to a strain of N. meningitidis of serogroup A that comprises lipooligosaccharide (LOS) particularly consisting of a lipid A, an inner core, and an L6 a chain, wherein the heptose II residue of the inner core has, at the O-3 position, a phosphoethanolamine (PEA) substituent and does not have any PEA substituent at the O-6 and O-7 positions. The abovementioned LOS or those from the mentioned strains can be used as vaccine antigens, in particular in multivalent, inter alia, bivalent, compositions in order to provide protection against major epidemiological complexes of N. meningitides, in particular of serogroup B.
摘要翻译：本发明特别涉及能够治疗或预防由脑膜炎奈瑟氏球菌，特别是血清组B引起的至少60％，优选75％的感染的多价疫苗组合物。为此，本发明基本上涉及脂多糖（LOS）脑膜炎奈瑟球菌特别由脂质A，内核和L6链组成，其中内核的肝素II残基在O-3位置和O-6或O-7位具有磷酸乙醇胺（PEA）取代基，以及能够表达这种LOS的脑膜炎奈瑟氏球菌菌株的结构。本发明还涉及血清组A的脑膜炎奈瑟氏球菌菌株，其包含特别由脂质A，内核和L6链构成的脂寡糖（LOS），其中内核的肝脏II残基在 O-3位，磷酸乙醇胺（PEA）取代基，O-6和O-7位没有任何PEA取代基。上述LOS或来自所述菌株的LOS可以用作疫苗抗原，特别是多价，特别是二价的组合物，以便提供防止脑膜炎奈瑟球菌，特别是血清群B的主要流行病学复合物的保护。

7. 发明专利

CA2761917C PROCEDE DE DETOXIFICATION DU LIPOPOLYSACCHARIDE (LPS) OU DU LIPIDE A DES BACTERIES A GRAM-NEGATIF 未知
公开(公告)号：CA2761917C
公开(公告)日：2018-06-12
申请号：CA2761917
申请日：2010-05-12
申请人： SANOFI PASTEUR
发明人： HAENSLER JEAN , DALENCON FRANCOIS , MOREAU MONIQUE , MISTRETTA NOELLE
IPC分类号： A61K39/39 , A61K9/127 , A61K39/00 , A61K39/095 , A61P31/04 , A61P37/04
摘要： L'invention a pour objet un procédé de détoxification du lipopolysaccharide (LPS) ou du lipide A d'une bactérie à Gram-négatif selon lequel on mélange le LPS ou le lipide A avec un lipide canonique et de manière optionnelle, un co-lipide, pour former un complexe dans lequel le LPS ou le lipide A est associé au lipide cationique. Selon des modes de préparation conventionnels, le lipide cationique avec le co-lipide, si ce dernier est présent, se structure(nt) en complexes, entre autres en liposomes. Lors de la préparation des complexes lipidiques, l'ajout du LPS ou du lipide A aboutit à l'association de ce dernier au lipide cationique, association dans laquelle le LPS ou le lipide A se trouve substantiellement détoxifié. Le LPS ou le lipide A détoxifié sous cette forme peut être alors utilisé comme antigène vaccinal ou à titre d'adjuvant.

8. 发明专利

CA2761924C VACCIN MENINGOCOQUE A BASE DE LIPOOLIGOSACCHARIDE (LOS) PROVENANT DE SOUCHES MODIFIEES DE NEISSERIA MENINGITIDIS D'IMMUNOTYPE L6 未知
公开(公告)号：CA2761924C
公开(公告)日：2017-10-31
申请号：CA2761924
申请日：2010-05-12
申请人： SANOFI PASTEUR
发明人： MISTRETTA NOELLE , MOREAU MONIQUE , RENAULD-MONGENIE GENEVIEVE , ROKBI BACHRA
IPC分类号： C12N1/21 , A61K39/095 , C12N15/63
摘要： L'invention a notamment pour objet des compositions vaccinales multivalentes susceptibles de traiter ou de prévenir au moins 60 %, de préférence 75 % des infections dues à Neisseria meningitidis notamment de sérogroupe B. A cette fin, l'invention fournit en particulier un lipooligosaccharide (LOS) de N. meningitidis constitué notamment d'un lipide A, d'un core interne, d'une chaîne a de type L6, dans lequel le résidu heptose II du core interne porte en position O-3 et en position O-6 ou O-7 un substituant phosphoéthanolamine (PEA) ainsi que la construction de la souche de N. meningitidis capable d'exprimer un tel LOS. L'invention porte également sur une souche de N. meningitidis de sérogroupe A qui possède un lipooligosaccharide (LOS) constitué notamment d'un lipide A, d'un core interne, d'une chaîne a de type L6, dans lequel le résidu heptose II du core interne porte en position O-3 un substituant phosphoéthanolamine (PEA) et ne porte pas de substituant PEA en positions O-6 et O-7. Les LOS cités ou provenant des souches mentionnées peuvent être utilisés comme antigènes vaccinaux, notamment dans des compositions multivalentes, i.a. bivalentes, afin d'offrir une protection à Pencontre des complexes épidémiologiques majeurs de N. meningitidis, notamment de sérogroupe B.

9. 发明专利

CA3000591A1 IMMUNOGENIC COMPOSITIONS AGAINST S. AUREUS 未知
公开(公告)号：CA3000591A1
公开(公告)日：2017-04-20
申请号：CA3000591
申请日：2016-10-13
申请人： SANOFI PASTEUR
发明人： DRIGUEZ PIERRE-ALEXANDRE , GUILLO NATHALIE , ROKBI BACHRA , MISTRETTA NOELLE , TALAGA PHILIPPE
IPC分类号： A61K39/085
摘要： The invention relates to a conjugate of a saccharide covalently bound to a carrier protein, wherein the saccharide comprises repetitive units of 1,5 ribitol phosphate in which all the ribitol residues are substituted by N-acetyl D-glucosaminyl residues at the 4-position, and wherein said N-acetyl D-glucosaminyl residues are exclusively in anomeric configuration a or are exclusively in anomeric configuration ß and wherein the carrier protein provides at least one epitope to the conjugate which is recognized by T helper lymphocytes.

10. 发明专利

AT520718T 未知
公开(公告)号：AT520718T
公开(公告)日：2011-09-15
申请号：AT04702733
申请日：2004-01-16
申请人： SANOFI PASTEUR
发明人： MISTRETTA NOELLE , DANVE EMILIE , MOREAU MONIQUE
IPC分类号： C08B37/00 , A61K39/09 , A61K39/385
摘要： New derivatives (I) of type 5 pneumococcal capsular protein are aminated at the terminal aldehyde group; and are characterized by their carbon-13 NMR spectrum and high performance anion exchange chromatography-pulsed amperometric detection (HPAEC-PAD) chromatogram. Also new are conjugates (A) of (I) with carrier proteins (P). New derivatives (I) of type 5 pneumococcal capsular protein are aminated at the terminal aldehyde group and have: (i) a carbon-13 NMR spectrum showing no resonance in the range 13-14 ppm (inclusive); and/or (ii) a high performance anion exchange chromatography-pulsed amperometric detection (HPAEC-PAD) chromatogram (obtained by elution of monosaccharides obtained by hydrolysis of (I) from a column of Carbopac PA 10 (RTM) in 18 mM sodium hydroxide solution at a flow rate of 1 ml per minute over 15 minutes) free of peaks between those of fucosamine and pneumosamine. Independent claims are also included for: (a) conjugates (A) of (I) with carrier proteins (P); and (b) the preparation of (I) (or more generally aminated type 5 pneumococcal capsular protein (I')) and (A).

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