EP0915987A2 - ACIDE POLY-$g(a)-L-ASPARTIQUE, ACIDE-POLY-$g(a)-L-GLUTAMIQUE ET COPOLYMERES DE L-ASP ET L-GLU, LEUR PROCEDE DE PREPARATION ET LEUR UTILISATION - Google Patents

ACIDE POLY-$g(a)-L-ASPARTIQUE, ACIDE-POLY-$g(a)-L-GLUTAMIQUE ET COPOLYMERES DE L-ASP ET L-GLU, LEUR PROCEDE DE PREPARATION ET LEUR UTILISATION

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Publication number
EP0915987A2
EP0915987A2 EP98922651A EP98922651A EP0915987A2 EP 0915987 A2 EP0915987 A2 EP 0915987A2 EP 98922651 A EP98922651 A EP 98922651A EP 98922651 A EP98922651 A EP 98922651A EP 0915987 A2 EP0915987 A2 EP 0915987A2
Authority
EP
European Patent Office
Prior art keywords
poly
asp
glu
acid
glutamic acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP98922651A
Other languages
German (de)
English (en)
Inventor
David A. Tirrell
Michael Del Grosso
Rainer Siegmeier
Andreas Bommarius
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Massachusetts UMass
Donlar Corp
Original Assignee
University of Massachusetts UMass
Donlar Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of Massachusetts UMass, Donlar Corp filed Critical University of Massachusetts UMass
Publication of EP0915987A2 publication Critical patent/EP0915987A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00—Preparation of peptides or proteins
    • C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof

Definitions

  • the terms polymer and copolymer comprise 5 to approx 200 amino acid units.
  • the invention also refers to a method for producing said polymers and copolymers by means of a microbiological process.
  • a further object of the invention is directed to the use of said polymers and copolymers as sequestering and dispersing agent.
  • Polyaspartic acids produced chemically from L- or DL-aspartic acid or suitable precursors, their salts as well as copolymers with other copolymerizable compounds are used as water-soluble sequestering agent and dispersing agents .
  • Polyamino acids and their salts are accessible in various methods of chemical production. Different methods of production and a few properties of polyamino acids are described, e.g., in Nachr. Chem. Tech. Lab., 1996, 44, 1167 - 1170 as well as in Hydrophylic Polymers, Performance with Environmental Acceptance, editor: J. Edward Glass, ACE, Washington, 1996, Commercial Poly (Aspartic Acid) and It's Uses, K.C. Low, A. P. Wheeler, L.P. Koskan, 99-111.
  • sodium salts of polyaspartic acids are obtained via the thermal polymerization of aspartic acid:
  • maleic acid anhydride is converted via maleic acid into fumaric acid, which is aminated in a following chemical or enzymatic method step to the ammonium salt of aspartic acid.
  • the free aspartic acid isolated therefrom is subjected to a solid-phase polymerization to the primary polymerization product.
  • suitable catalysts such as phosphoric acid.
  • maleic acid anhydride or maleic acid anhydride derivatives such as maleic acid ammonium salts, maleic amide acid, maleic amide acid ammonium salts can be thermally polymerized to a primary polymerization product in the presence of nitrogen- containing compounds such as ammonia but also of ammonium salts such as ammonium carbonate.
  • the primarily formed polymerization products are distinguished by polysuccinimide structural elements which result in subsequent hydrolysis in polyaspartic acids with ⁇ - and ⁇ - linked aspartic acid units.
  • the ⁇ / ⁇ ratio can be determined via NMR spectroscopic methods.
  • An ⁇ / ⁇ ratio of approximately 30:70 which can be influenced only slightly, results for all polyaspartic acids obtained according to the thermal polymerization methods and alkaline hydrolysis described here.
  • the main production methods described up to the present determine the structural parameters such as, e.g., the molecular weight, the linearity and the properties correlating therewith as well as the action in various applications and the biological degradability.
  • the EP-patent application 256 423 of Chisso discloses a process for the manufacture of ⁇ -poly-L-lysine, derived from Streptomyces albulus subspecies lysinopolymerus No. 346-D.
  • the process for the manufacture of of ⁇ -poly-L- lysine is characterized by the addition of sugar to the culturing medium.
  • the EP-A 0 557 954 refers to a process for the manufacture of ⁇ -poly-L-lysine with immobilized bacterial cells under aerobic conditions.
  • An isolated ⁇ -polyglutamate hydrolase is known from the EP- A 559 175 and US 5,356,805. Takeda Chemical discloses in the EP-A 410 638 a process to the manufacture of polyglutamic acid.
  • the microorganisms used for the polymerisation of L-glutamic acid were bacteria such as Bacillus subtilis or Bacillus licheniformis .
  • the product contains poly- ⁇ -L-glutamic acid with a wide spectrum of Glu-units in the polymer.
  • Poly- ⁇ -L-Glu has not been synthesized either directly through microbiological methods.
  • chemically generated poly-Glu the same observations and arguments hold as for chemcally generated poly-Asp.
  • the polymerisation degree is well defined and only dependent on the length of the polynucleotide which is used in the microbiological manufacturing process .
  • the task to find the a. m. polymers consisting of poly- ⁇ -L- Asp, poly- ⁇ -L-glu or copolymers of both amino acids that feature improved properties with respect to biological degradability and discoloration is solved by employing a oligonucleotide construct that encodes the desired sequence of Asp polymers (or Asp/Glu polymers) .
  • the amino acid Glu is encoded by two codons , GAA and GAG. In certain organisms such as E. coli , Glu is preferably encoded by GAA. Asp is encoded by two codons as well, GAC and GAT. The latter is preferred in many organisms such as E. coli .
  • the oligonucleotide construct encoding for the desired Asp length (or Asp/Glu length) is cloned into a plasmid.
  • Cells of the desired host cell line such as Escherichia coli , Bacillus subtilis ox Corynebacterium glutamicum, are transformed with the altered plasmids, and the genetic information expressed.
  • the oligonucleotide duplex which encodes the desired Glu or Asp or Glu/Asp amino acid sequence of the predetermined number of amino acid units of each polymer chain is synthesized on a DNA synthesizer.
  • the oligonucleotides are purified by electrophoresis on a polyacrylamide denaturing gel, annealed, enzymatically phosphorylated at the 5' termini, and ligated with BamUI -digested, phosphatase- treated plasmid pUC18.
  • the sequence of the insert is verified by a technique such as the Sanger dideoxy sequencing strategy.
  • E. coli strains are transformed with the recombinant plasmid and marked by an appropriate technique such as insertional inactivation of a gene or resistance against antibiotics.
  • a Glu/Asp sequence which by itself is a multimer of a simpler Glu/Asp sequence the recombinant plasmid is digested and affords a DNA fragment encoding the desired poly-Glu/Asp sequence.
  • This DNA is purified on a polyacrylamide gel and self-ligated in head- to-tail fashion with T4 DNA ligase to yield a population of multimers. A portion of the ligation mixture is analyzed on a 1.5% agarose gel. The ligation mixture is cloned into a plasmid such as pUC803 or pUC18. E. coli cells are then transformed with the recombinant plasmids .
  • a plasmid containing the repeat units of the DNA monomer is isolated, and the nucleotide sequence confirmed by sequencing of the double-stranded DNA.
  • the BamRI segment is recovered, purified and inserted into a suitable expression vector.
  • the ligation mix is used to transform E. coli cells, and the presence and orientation of the insert are checked by digestion with restriction enzymes BamHI and Aval , respectively.
  • the fusion protein is purified by standard techniques such as affinity chromatography, precipitation in organic solvent, and the like. Electrophoretic purification on a non-denaturing polyacrylamide gel affords a product which migrates as a single band at the expected molecular weight and which yields amino acid analyses consistent with the desired sequence .
  • the new aminoacid polymers and copolymers have many fold usefulness in any kind of water treatment and relevant processes :
  • Polyaspartic acid Na-salts have a dispersing action which reinforces the primary washing power.
  • Polyaspartic acids and their salts are used in washing [detergent] - and cleaning agents.
  • the detergents can be powdery or also be present in liquid form.
  • the composition of the washing- and cleaning agent formulations can be very different. Washing- and cleaning agent formulations customarily contain 2 to 50 % by weight surfactants and optional builders. This data applies both to liquid and to powdery detergents. Washing- and cleaning agent formulations customary in Europe, the USA and Japan are to be found, e.g., in Chemical and Engn. News, vol. 67, 35 (1989) in table form.
  • washing- and cleaning agents can be gathered from Ullmanns Encyklopadie der ischen Chemie, Verlag Chemie, Weinheim, 1983, 4 edition, pp. 63 - 160.
  • the use of polyaspartic acid in washing- and cleaning agents is described, among other places, in WO 95/16020, WO 95/16726, DE 44 30 520, DE 44 28 638, DE 44 28 597.
  • Inhibitors are used in cooling-water circuits, in the treating of boiler and feed water and in the desalination of see water for avoiding and eliminating precipates and coatings .
  • Polyaspartic acids prevent and/or delay the crystallization of alkaline-earth salts such as calcium carbonate, calcium sulfate, etc. The action thereby is far below the concentrations necessary for complex formation (threshold effect) .
  • Polyaspartic acid synthezised by thermal condensation of L-aspartic acid, is described as an inhibitor of corrosion in Little et al .
  • thermal Polyaspartate surface reactive peptides and polymers, pp. 263-279, ACS Symposium Series 444 (1990) .
  • Thermal polyaspartate binds to surfaces of mild steel and moderately supresses both anodic and cathodic corrosion reactions .
  • the see water contains sulfate.
  • the petroleum is accompanied by formation water containing barium ions and strontium ions. If the formation water and the see water mix, poorly soluble Ba sulfates and Sr sulfates form which may possibly clog boreholes and pipelines. Polyaspartic acids prevent and/or delay the crystallization of the precipitates so that the undesired coating formations do not occur.
  • Natural gas standing under pressure has a residual moisture content in the winning process. Salts are dissolved in this residual moisture. During the winning [extraction] process, especially during the expansion of the gas, a critical pressure is dropped below which results in a crystallizing out of the salts and a clogging of the porous sandstone .
  • Polyaspartic acids prevent and/or delay the crystallization of the salts in both instances on account of their dispersing properties.
  • Amino acid analyses were carried out on an apparatus like, for example, the Applied Biosystems 420/130A derivatizer/analyzer device.
  • Oligonucleotides were prepared by means of ⁇ - cyanoethylphosphorus amidite chemistry on a synthesizer like Biosearch Model 8700 and purified by means of 10 % denaturing polyacrylamid gel electrophoresis .
  • the purified oligonucleotides were annealed at 80 °C and allowed to cool off for several hours until room temperature.
  • the double strand was phosphorylated by T4-polynucleotide kinase, precipitated in ethanol and dried in a vacuum.
  • the double strand was ligated into a plasmid like pUC18 which had been cleaved by restriction endonucleases like, e.g., Eco RT or Bam HI and transformed in cells like, e.g., E. coli DH5 ⁇ F' .
  • restriction endonucleases like, e.g., Eco RT or Bam HI
  • cells like, e.g., E. coli DH5 ⁇ F' .
  • the cells were cultivated at 37 °C on a medium like 2xYT under the addition of ampicillin (about 0.2 mg/ml) , isopropyl- ⁇ -D-thiogalactopyranoside (IPTG) (0.025 mg/ml) and a chromogenic substrate like 5-bromo-4- chloro-3-indolyl- ⁇ -D-galactopyranoside (called X-Gal here) which turned blue in the case of cells with active ⁇ - galactosidase gene but remained white in the case of cells which had lost the corresponding activity by inserting inactivation of the ⁇ -galactosidase gene.
  • ampicillin about 0.2 mg/ml
  • IPTG isopropyl- ⁇ -D-thiogalactopyranoside
  • X-Gal 5-bromo-4- chloro-3-indolyl- ⁇ -D-galactopyranoside
  • Plasmid DNA from the white transformants is sequenced in order to verify the identity of the inserted DNA, e.g. by sequenase 2.0 of Amersham Life Sciences. After isolation of the recombinant plasmid from the 2xYT culture medium the DNA was digested by the restriction endonuclease BanI and the fragments separated by non-denaturing PAGE and the interesting DNA monomer washed down.
  • the purified DNA monomer is self- ligated with T4 DNA ligase in order to produce a distribution of multimers.
  • the multimers are separated by electrophoresis and ligated into a dephosphorylated, high copy number cloning vector digested with BanI.
  • the recombinant plasmid was transformed into a strain like E. coli. Transformants are analyzed by analysis of the restriction enzyme digestion pattern and the desired DNA chain length (with the desired number of repeating units) selected. Construction of the bacterial expression vector
  • the recombinant plasmids from the transformants were digested with restriction endonucleases like BamHI , the multimer fragments separated on 1 % agarose gel electrophoresis and recovered by extraction e.g. in phenol, phenol/chloroform or ethanol. Transformants were checked by digestion with nucleases like Aval for the presence and orientation of multimers. Transformants with correct sequence were used for the transformation of the expression host.
  • the fusion protein was obtained by centrifugation after the thawed [defrosted] cells had been treated successively twice with EDTA/surfactant , then with lipase, finally with organic solvents (chloroform/methanol) and were finally washed with water.
  • An affinity chromatography then selectively follows, e.g., via glutathione-linked sepharose . Cleaving of the fusion protein
  • the fusion protein is preferably cleaved by the bromocyanogen method (cf . B.J. Smith, Methods in Biology, New Protein Techniques, Humana, Clifton, NH, 1988) . After the cleaving the solvent is drawn off by vacuum evaporation and the insoluble portion recovered by centrifugation and dried by lyophilization.

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Polyamides (AREA)

Abstract

L'invention concerne de l'acide poly-α-L-aspartique (= poly-L-α-Asp), de l'acide poly-α-L-glutamique et de nouveaux copolymères de L-Asp et L-Glu présentant essentiellement des liaisons α, ainsi que des sels desdits polymères et copolymères. Un procédé servant à préparer ces acides polyaminés consiste à mettre en application un produit de recombinaison d'oligonucléotide codant la séquence du polymère souhaité, à cloner cet oligonucléotide en plasmide, à transformer les cellules hôtes au moyen du plasmide et à exprimer l'information génétique. Etant donné leur excellente dégradabilité biologique, on peut utiliser ces nouveaux acides poly-α-L-aminés en tant qu'adjuvants combinés, qu'agents chélatants ou qu'inhibiteurs de corrosion.
EP98922651A 1997-04-21 1998-04-06 ACIDE POLY-$g(a)-L-ASPARTIQUE, ACIDE-POLY-$g(a)-L-GLUTAMIQUE ET COPOLYMERES DE L-ASP ET L-GLU, LEUR PROCEDE DE PREPARATION ET LEUR UTILISATION Withdrawn EP0915987A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US4472797P 1997-04-21 1997-04-21
US44727P 1997-04-21
PCT/EP1998/001996 WO1998048032A2 (fr) 1997-04-21 1998-04-06 ACIDE POLY-α-L-ASPARTIQUE, ACIDE-POLY-α-L-GLUTAMIQUE ET COPOLYMERES DE L-ASP ET L-GLU, LEUR PROCEDE DE PREPARATION ET LEUR UTILISATION

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EP0915987A2 true EP0915987A2 (fr) 1999-05-19

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Families Citing this family (80)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8802820B2 (en) 2004-11-12 2014-08-12 Xencor, Inc. Fc variants with altered binding to FcRn
JP4652414B2 (ja) 2004-11-12 2011-03-16 ゼンコー・インコーポレイテッド ＦｃＲｎとの変化した結合を有するＦｃ変異体
PL2808343T3 (pl) 2007-12-26 2019-11-29 Xencor Inc Warianty Fc ze zmienionym wiązaniem do FcRn
CN110317272A (zh) 2008-10-14 2019-10-11 霍夫曼-拉罗奇有限公司 免疫球蛋白变体及其用途
AU2009329866B2 (en) 2008-12-23 2016-09-29 Genentech, Inc. Immunoglobulin variants with altered binding to protein A
BRPI1010297A2 (pt) 2009-04-07 2017-06-06 Roche Glycart Ag anticorpos biespecíficos trivalentes.
US9676845B2 (en) 2009-06-16 2017-06-13 Hoffmann-La Roche, Inc. Bispecific antigen binding proteins
US20120302737A1 (en) 2009-09-16 2012-11-29 Genentech, Inc. Coiled coil and/or tether containing protein complexes and uses thereof
WO2011097527A2 (fr) 2010-02-04 2011-08-11 Xencor, Inc. Immunoprotection de fractions thérapeutiques avec des régions fc améliorées
TW201138821A (en) 2010-03-26 2011-11-16 Roche Glycart Ag Bispecific antibodies
CA2807278A1 (fr) 2010-08-24 2012-03-01 F. Hoffmann - La Roche Ag Anticorps bispecifiques comprenant un fragment fv stabilise par bisulfure
SG191153A1 (en) 2010-12-23 2013-07-31 Hoffmann La Roche Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery
WO2012116927A1 (fr) 2011-02-28 2012-09-07 F. Hoffmann-La Roche Ag Protéines monovalentes de liaison à l'antigène
RU2607038C2 (ru) 2011-02-28 2017-01-10 Ф. Хоффманн-Ля Рош Аг Антигенсвязывающие белки
CN103476795B (zh) 2011-03-29 2016-07-06 罗切格利卡特公司 抗体Fc变体
CN104105711B (zh) 2012-02-10 2018-11-30 弗·哈夫曼-拉罗切有限公司 单链抗体及其他异多聚体
WO2013192131A1 (fr) 2012-06-21 2013-12-27 Indiana University Research And Technology Corporation Polypeptides de fusion de région fc de polypeptide ligand du récepteur d'incrétine et conjugués à fonction effectrice fc modifiée
CA2871882A1 (fr) 2012-06-27 2014-01-03 F. Hoffmann-La Roche Ag Methode de fabrication de conjugues d'anticorps a region fc comprenant au moins une entite de liaison qui se lie specifiquement a une cible et leurs utilisations
CN104395339A (zh) 2012-06-27 2015-03-04 弗·哈夫曼-拉罗切有限公司 用于选择并产生含有至少两种不同结合实体的定制高度选择性和多特异性靶向实体的方法及其用途
EA032192B1 (ru) 2012-07-13 2019-04-30 Роше Гликарт Аг Биспецифическое антитело к vegf/ang-2, нуклеиновая кислота, кодирующая это антитело, вектор, содержащий нуклеиновую кислоту, клетка-хозяин, способ получения биспецифического антитела и содержащая его фармацевтическая композиция
US20140161790A1 (en) 2012-11-19 2014-06-12 Xencor, Inc. Engineered immunoglobulins with extended in vivo half-life
US9260527B2 (en) 2013-03-15 2016-02-16 Sdix, Llc Anti-human CXCR4 antibodies and methods of making same
AU2014232416B2 (en) 2013-03-15 2017-09-28 Xencor, Inc. Modulation of T Cells with Bispecific Antibodies and FC Fusions
EP2951203B1 (fr) 2013-03-15 2019-05-22 Xencor, Inc. Protéines hétérodimériques
RU2687043C2 (ru) 2013-04-29 2019-05-06 Ф. Хоффманн-Ля Рош Аг МОДИФИЦИРОВАННЫЕ АСИММЕТРИЧНЫЕ АНТИТЕЛА, СВЯЗЫВАЮЩИЕ Fc-РЕЦЕПТОР, И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
SG11201508911PA (en) 2013-04-29 2015-11-27 Hoffmann La Roche Human fcrn-binding modified antibodies and methods of use
BR112016006929A2 (pt) 2013-10-11 2017-09-19 Hoffmann La Roche Anticorpo, ácido nucleico, vetor de expressão, célula hospedeira, métodos de preparação de anticorpo, de tratamento de pacientes e de geração de um anticorpo, composição farmacêutica e uso do anticorpo
JP2017504598A (ja) 2013-12-20 2017-02-09 インディアナ ユニヴァーシティ リサーチ アンド テクノロジー コーポレイション 脂質化インクレチン受容体リガンドヒト免疫グロブリンｆｃ−領域融合ポリペプチド
CN110903398B (zh) 2014-01-15 2023-08-15 豪夫迈·罗氏有限公司 具有修饰的FCRN和保持的蛋白A结合性质的Fc区变体
BR112016022385A2 (pt) 2014-03-28 2018-06-19 Xencor, Inc anticorpos específicos que se ligam a cd38 e cd3
KR20170076697A (ko) 2014-11-06 2017-07-04 에프. 호프만-라 로슈 아게 개질된 FCRN-결합 특성 및 단백질 A-결합 특성을 가진 Fc-영역 변이체
EP3611188B1 (fr) 2014-11-06 2022-05-04 F. Hoffmann-La Roche AG Variants de zone fc présentant des propriétés du ligand fcrn modifié et procédés d'utilisation
EA037065B1 (ru) 2014-11-26 2021-02-01 Ксенкор, Инк. Гетеродимерные антитела, связывающие cd3 и cd38
TN2017000223A1 (en) 2014-11-26 2018-10-19 Xencor Inc Heterodimeric antibodies that bind cd3 and tumor antigens
US20160176969A1 (en) 2014-11-26 2016-06-23 Xencor, Inc. Heterodimeric antibodies including binding to cd8
ES2764111T3 (es) 2014-12-03 2020-06-02 Hoffmann La Roche Anticuerpos multiespecíficos
WO2016141387A1 (fr) 2015-03-05 2016-09-09 Xencor, Inc. Modulation de lymphocytes t avec des anticorps bispécifiques et des hybrides fc
CN115536750A (zh) 2015-05-08 2022-12-30 森科股份有限公司 结合cd3和肿瘤抗原的异二聚体抗体
WO2016207304A2 (fr) 2015-06-26 2016-12-29 Mab Discovery Gmbh Anticorps monoclonaux anti-il-1racp
CN114920846A (zh) 2015-10-29 2022-08-19 豪夫迈·罗氏有限公司 抗变体Fc区抗体及使用方法
KR102523682B1 (ko) 2016-05-02 2023-04-19 에프. 호프만-라 로슈 아게 콘톨스바디 - 단쇄 표적 결합제
EP3241845A1 (fr) 2016-05-06 2017-11-08 MAB Discovery GmbH Anticorps anti-il-1r3 humanisés
WO2017210485A1 (fr) 2016-06-01 2017-12-07 Xencor, Inc. Anticorps bispécifiques qui se lient à cd20 et cd3 destinés à être utilisés dans le traitement d'un lymphome
WO2017210443A1 (fr) 2016-06-01 2017-12-07 Xencor, Inc. Anticorps bispécifiques qui lient cd123 et cd3
IL301682A (en) 2016-08-17 2023-05-01 Compugen Ltd Antibodies against TIGIT, antibodies against PVRIG and their combinations
WO2018045110A1 (fr) 2016-08-30 2018-03-08 Xencor, Inc. Anticorps immunomodulateurs bispécifiques qui se lient à des récepteurs de costimulation et de points de contrôle
AU2017342560B2 (en) 2016-10-14 2022-03-17 Xencor, Inc. IL15/IL15Ralpha heterodimeric Fc-fusion proteins
WO2018129522A1 (fr) 2017-01-09 2018-07-12 Torch Therapeutics Agents thérapeutiques bispécifiques conditionnellement efficaces
EP3401332A1 (fr) 2017-05-08 2018-11-14 MAB Discovery GmbH Anticorps anti-il-1r3 destinés à être utilisés dans des conditions inflammatoires
SG10202111336RA (en) 2017-06-01 2021-11-29 Compugen Ltd Triple combination antibody therapies
WO2018223004A1 (fr) 2017-06-01 2018-12-06 Xencor, Inc. Anticorps bispécifiques se liant à cd20 et cd3
JP2020522498A (ja) 2017-06-01 2020-07-30 ゼンコー・インコーポレイテッドＸｅｎｃｏｒ、 Ｉｎｃ． Ｃｄ１２３ ｃｄ３に結合する二重特異性抗体
WO2019006472A1 (fr) 2017-06-30 2019-01-03 Xencor, Inc. Protéines de fusion fc hétérodimères ciblées contenant il-15/il-15ra et domaines de liaison à l'antigène
JP2021500930A (ja) 2017-11-01 2021-01-14 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ Ｃｏｍｐボディ−多価標的結合物質
US11319355B2 (en) 2017-12-19 2022-05-03 Xencor, Inc. Engineered IL-2 Fc fusion proteins
UY38080A (es) 2018-02-08 2019-08-30 Amgen Inc FORMULACIÓN FARMACÉUTICA DE pH BAJO
CN112105645A (zh) 2018-04-18 2020-12-18 Xencor股份有限公司 Il-15/il-15ra异二聚体fc融合蛋白及其用途
JP2021520829A (ja) 2018-04-18 2021-08-26 ゼンコア インコーポレイテッド ＩＬ−１５／ＩＬ−１５ＲＡ Ｆｃ融合タンパク質およびＴＩＭ−３抗原結合ドメインを含む、ＴＩＭ−３標的化ヘテロ二量体融合タンパク質
WO2019204665A1 (fr) 2018-04-18 2019-10-24 Xencor, Inc. Protéines de fusion hétérodimères ciblant pd-1 contenant des protéines de fusion fc d'il-15/il-15ra, domaines de liaison à l'antigène pd-1 et utilisations associées
JP7366056B2 (ja) 2018-04-18 2023-10-20 ゼンコア インコーポレイテッド ＩＬ－１５／ＩＬ－１５ＲＡ Ｆｃ融合タンパク質およびＬＡＧ－３抗原結合ドメインを含む、ＬＡＧ－３を標的とするヘテロ二量体融合タンパク質
KR20210005683A (ko) 2018-04-27 2021-01-14 노파르티스 아게 Cd123 및 cd3에 결합하는 이중특이적 항체의 투약
AU2019276578A1 (en) 2018-06-01 2021-01-14 Compugen Ltd Anti-PVRIG/anti-TIGIT bispecific antibodies and methods of use
EP3801617A1 (fr) 2018-06-01 2021-04-14 Novartis Ag Dosage d'un anticorps bispécifique qui se lie à cd123 et cd3
KR20210028204A (ko) 2018-07-02 2021-03-11 암젠 인크 항-steap1 항원 결합 단백질
WO2020018556A1 (fr) 2018-07-16 2020-01-23 Amgen Inc. Procédé de traitement du myélome multiple
AU2019359475A1 (en) 2018-10-12 2021-05-20 Xencor, Inc. PD-1 targeted IL-15/IL-15Ralpha Fc fusion proteins and uses in combination therapies thereof
US11618776B2 (en) 2018-12-20 2023-04-04 Xencor, Inc. Targeted heterodimeric Fc fusion proteins containing IL-15/IL-15RA and NKG2D antigen binding domains
CN113710324A (zh) 2019-01-23 2021-11-26 千禧制药公司 抗cd38抗体
TW202128757A (zh) 2019-10-11 2021-08-01 美商建南德克公司 具有改善之特性的 PD-1 標靶 IL-15/IL-15Rα FC 融合蛋白
WO2021113831A1 (fr) 2019-12-05 2021-06-10 Compugen Ltd. Anticorps anti-pvrig et anti-tigit pour élimination de tumeurs à base de cellules nk améliorées
TW202136318A (zh) 2020-01-28 2021-10-01 美商建南德克公司 用於治療癌症的 IL15/IL15R α 異二聚體 Fc 融合蛋白質
TW202146452A (zh) 2020-02-28 2021-12-16 瑞士商諾華公司 結合ｃｄ１２３和ｃｄ３之雙特異性抗體的給藥
US20240002509A1 (en) 2020-11-06 2024-01-04 Novartis Ag ANTIBODY Fc VARIANTS
JP2023554456A (ja) 2020-12-18 2023-12-27 チューハイ トリノマブ ファーマシューティカル カンパニー リミテッド 呼吸器合胞体ウイルスに特異的に結合する分子
WO2022140701A1 (fr) 2020-12-24 2022-06-30 Xencor, Inc. Protéines de fusion hétérodimères ciblées par icos contenant des protéines de fusion fc d'il-15/il-15ra et domaines de liaison à l'antigène icos
EP4376869A1 (fr) 2021-07-28 2024-06-05 Genentech, Inc. Protéines de fusion à fc hétérodimères il15/il15r alpha pour le traitement de cancers du sang
EP4380596A1 (fr) 2021-08-04 2024-06-12 Genentech, Inc. Protéines de fusion hétérodimères avec fc et il15/il15r alpha servant à faire proliférer des lymphocytes nk dans le traitement de tumeurs solides
EP4388014A1 (fr) 2021-08-19 2024-06-26 F. Hoffmann-La Roche AG Anticorps à région fc anti-variant multivalente et méthode d'utilisation
WO2023175498A1 (fr) 2022-03-17 2023-09-21 Pfizer Inc. Enzymes de dégradation d'igg améliorées et leurs procédés d'utilisation
WO2023196905A1 (fr) 2022-04-07 2023-10-12 Xencor, Inc. Protéines de fusion hétérodimères ciblant lag-3 contenant des protéines de fusion fc d'il-15/il-15ra et domaines de liaison à l'antigène de lag-3

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2068971B (en) * 1980-01-30 1983-06-08 Searle & Co Recombinant dna techniques
EP0410638A3 (en) * 1989-07-26 1991-06-05 Takeda Chemical Industries, Ltd. Method for producing polyglutamic acid or a salt thereof
US5498410A (en) * 1991-04-22 1996-03-12 Gleich; Gerald J. Method for the treatment of eosinophil-associated conditions with anionic polymers
US5371179A (en) * 1992-07-10 1994-12-06 Rohm And Haas Company Polysuccinimide polymers and process for preparing polysuccinimide polymers
DE4342316A1 (de) * 1993-12-11 1995-06-14 Basf Ag Verwendung von Polyasparaginsäure in Wasch- und Reinigungsmitteln

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9848032A3 *

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