BISPECIFIC ANTIGEN-BINDING PROTEINS

FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to biotechnology and represents a method for producing a bispecific antigen-binding protein containing: two light chains and two heavy chains of a full-length antibody containing two Fab fragments and specifically binding to the first antige...

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Hauptverfasser: VOL'FGANG SHEHFER, JURGEN MIKHAEHL' SHANTSER, JERG TOMAS REGULA, KRISTIAN KLAJN, ZABINE IMKHOF-JUNG
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creator VOL'FGANG SHEHFER
JURGEN MIKHAEHL' SHANTSER
JERG TOMAS REGULA
KRISTIAN KLAJN
ZABINE IMKHOF-JUNG
description FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to biotechnology and represents a method for producing a bispecific antigen-binding protein containing: two light chains and two heavy chains of a full-length antibody containing two Fab fragments and specifically binding to the first antigen; and two supplementary Fab fragments of the antibody, which specifically binds to the second antigen, wherein the above both supplementary Fab fragments are fused by means of a connector peptide to C- or N-terminals of the heavy chains specified in sub-clause a); wherein the connector peptide represents (Gly-x-Ser)n, or (Gly-x-Ser)nGlym(x = 3, n = 3, 4, 5 or 6 and m = 0, 1, 2 or 3), or (x = 4, n = 2, 3, or 5 and m = 0, 1, 2 or 3) and wherein the Fab fragments are modified as follows: I) in both of the Fab fragments specified in sub-clause a), or in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, and/or constant domains CL and CH1 are substituted by each other; II) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other, and constant domains CL and CH1 are substituted by each other, and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, or constant domains CL and CH1 are substituted by each other; III) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other, or constant domains CL and CH1 are substituted by each other, and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, and constant domains CL and CH1 are substituted by each other; IV) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other and in both of the Fab fragments specified in sub-clause b), constant domains CL and CH1 are substituted by each other; or V) in both of the Fab fragments specified in sub-clause a), constant domains CL and CH1 are substituted by each other and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other; whereas the method involves the stages of: a) transforming a host cell by means of expression vectors, which contain nucleic acid molecules coding the above bispecific antigen-binding protein; b) culturing the host cell in the environment, which enable synthes
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fullrecord <record><control><sourceid>epo_EVB</sourceid><recordid>TN_cdi_epo_espacenet_RU2573914C2</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>RU2573914C2</sourcerecordid><originalsourceid>FETCH-epo_espacenet_RU2573914C23</originalsourceid><addsrcrecordid>eNrjZFB28gwOcHX2dPN0VnD0C_F0d_XTdfL0c_H0c1cICPIPcfX0C-ZhYE1LzClO5YXS3AwKbq4hzh66qQX58anFBYnJqXmpJfFBoUam5saWhibORsZEKAEAHzwijQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>patent</recordtype></control><display><type>patent</type><title>BISPECIFIC ANTIGEN-BINDING PROTEINS</title><source>esp@cenet</source><creator>VOL'FGANG SHEHFER ; JURGEN MIKHAEHL' SHANTSER ; JERG TOMAS REGULA ; KRISTIAN KLAJN ; ZABINE IMKHOF-JUNG</creator><creatorcontrib>VOL'FGANG SHEHFER ; JURGEN MIKHAEHL' SHANTSER ; JERG TOMAS REGULA ; KRISTIAN KLAJN ; ZABINE IMKHOF-JUNG</creatorcontrib><description>FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to biotechnology and represents a method for producing a bispecific antigen-binding protein containing: two light chains and two heavy chains of a full-length antibody containing two Fab fragments and specifically binding to the first antigen; and two supplementary Fab fragments of the antibody, which specifically binds to the second antigen, wherein the above both supplementary Fab fragments are fused by means of a connector peptide to C- or N-terminals of the heavy chains specified in sub-clause a); wherein the connector peptide represents (Gly-x-Ser)n, or (Gly-x-Ser)nGlym(x = 3, n = 3, 4, 5 or 6 and m = 0, 1, 2 or 3), or (x = 4, n = 2, 3, or 5 and m = 0, 1, 2 or 3) and wherein the Fab fragments are modified as follows: I) in both of the Fab fragments specified in sub-clause a), or in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, and/or constant domains CL and CH1 are substituted by each other; II) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other, and constant domains CL and CH1 are substituted by each other, and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, or constant domains CL and CH1 are substituted by each other; III) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other, or constant domains CL and CH1 are substituted by each other, and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, and constant domains CL and CH1 are substituted by each other; IV) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other and in both of the Fab fragments specified in sub-clause b), constant domains CL and CH1 are substituted by each other; or V) in both of the Fab fragments specified in sub-clause a), constant domains CL and CH1 are substituted by each other and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other; whereas the method involves the stages of: a) transforming a host cell by means of expression vectors, which contain nucleic acid molecules coding the above bispecific antigen-binding protein; b) culturing the host cell in the environment, which enable synthesising a molecule of this bispecific antigen-binding protein; and c) recovering the molecule of the above bispecific antigen-binding protein from the above culture.EFFECT: invention enables producing the bispecific antibody having the structure described above.7 cl, 7 dwg, 3 tbl, 3 ex Изобретение относится к области биотехнологии и представляет собой способ получения биспецифического антигенсвязывающего белка, содержащего: две легкие цепи и две тяжелые цепи полноразмерного антитела, включающего два Fab-фрагмента и специфически связывающегося с первым антигеном; и два дополнительных Fab-фрагмента антитела, которое специфически связывается со вторым антигеном, где указанные дополнительные Fab-фрагменты оба слиты посредством пептида-коннектора с С- или N-концами тяжелых цепей, указанных в подпункте а); где пептидом-коннектором является (Gly-x-Ser)n, или (Gly-x-Ser)nGlym(х=3, n=3, 4, 5 или 6 и m=0,1, 2 или 3), или (х=4, n=2,3, или 5 и m=0, 1, 2 или 3) и где в Fab-фрагментах осуществлены следующие модификации: I) в обоих Fab-фрагментах, указанных в подпункте а), или в обоих Fab-фрагментах, указанных в подпункте б), вариабельные домены VL и VH заменены друг на друга и/или константные домены CL и СН1 замены друг на друга; II) в обоих Fab-фрагментах, указанных в подпункте а), вариабельные домены VL и VH заменены друг на друга и константные домены CL и СН1 заменены друг на друга, и в обоих Fab-фрагментах, указанных в подпункте б), вариабельные домены VL и VH заменены друг на друга или константные домены CL и СН1 заменены друг на друга; III) в обоих Fab-фрагментах, указанных в подпункте а), вариабельные домены VL и VH заменены друг на друга или константные домены CL и СН1 заменены друг на друга, и в обоих Fab-фрагментах, указанных в подпункте б), вариабельные домены VL и VH заменены друг на друга и константные домены CL и СН1 заменены друг на друга; IV) в обоих Fab-фрагментах, указанных в подпункте а), вариабельные домены VL и VH заменены друг на друга и в обоих Fab-фрагментах, указанных в подпункт</description><language>eng ; rus</language><subject>BEER ; BIOCHEMISTRY ; CHEMISTRY ; ENZYMOLOGY ; FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE ; METALLURGY ; MICROBIOLOGY ; MUTATION OR GENETIC ENGINEERING ; ORGANIC CHEMISTRY ; PEPTIDES ; SPIRITS ; VINEGAR ; WINE</subject><creationdate>2016</creationdate><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&amp;date=20160127&amp;DB=EPODOC&amp;CC=RU&amp;NR=2573914C2$$EHTML$$P50$$Gepo$$Hfree_for_read</linktohtml><link.rule.ids>230,308,780,885,25563,76418</link.rule.ids><linktorsrc>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&amp;date=20160127&amp;DB=EPODOC&amp;CC=RU&amp;NR=2573914C2$$EView_record_in_European_Patent_Office$$FView_record_in_$$GEuropean_Patent_Office$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>VOL'FGANG SHEHFER</creatorcontrib><creatorcontrib>JURGEN MIKHAEHL' SHANTSER</creatorcontrib><creatorcontrib>JERG TOMAS REGULA</creatorcontrib><creatorcontrib>KRISTIAN KLAJN</creatorcontrib><creatorcontrib>ZABINE IMKHOF-JUNG</creatorcontrib><title>BISPECIFIC ANTIGEN-BINDING PROTEINS</title><description>FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to biotechnology and represents a method for producing a bispecific antigen-binding protein containing: two light chains and two heavy chains of a full-length antibody containing two Fab fragments and specifically binding to the first antigen; and two supplementary Fab fragments of the antibody, which specifically binds to the second antigen, wherein the above both supplementary Fab fragments are fused by means of a connector peptide to C- or N-terminals of the heavy chains specified in sub-clause a); wherein the connector peptide represents (Gly-x-Ser)n, or (Gly-x-Ser)nGlym(x = 3, n = 3, 4, 5 or 6 and m = 0, 1, 2 or 3), or (x = 4, n = 2, 3, or 5 and m = 0, 1, 2 or 3) and wherein the Fab fragments are modified as follows: I) in both of the Fab fragments specified in sub-clause a), or in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, and/or constant domains CL and CH1 are substituted by each other; II) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other, and constant domains CL and CH1 are substituted by each other, and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, or constant domains CL and CH1 are substituted by each other; III) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other, or constant domains CL and CH1 are substituted by each other, and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, and constant domains CL and CH1 are substituted by each other; IV) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other and in both of the Fab fragments specified in sub-clause b), constant domains CL and CH1 are substituted by each other; or V) in both of the Fab fragments specified in sub-clause a), constant domains CL and CH1 are substituted by each other and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other; whereas the method involves the stages of: a) transforming a host cell by means of expression vectors, which contain nucleic acid molecules coding the above bispecific antigen-binding protein; b) culturing the host cell in the environment, which enable synthesising a molecule of this bispecific antigen-binding protein; and c) recovering the molecule of the above bispecific antigen-binding protein from the above culture.EFFECT: invention enables producing the bispecific antibody having the structure described above.7 cl, 7 dwg, 3 tbl, 3 ex Изобретение относится к области биотехнологии и представляет собой способ получения биспецифического антигенсвязывающего белка, содержащего: две легкие цепи и две тяжелые цепи полноразмерного антитела, включающего два Fab-фрагмента и специфически связывающегося с первым антигеном; и два дополнительных Fab-фрагмента антитела, которое специфически связывается со вторым антигеном, где указанные дополнительные Fab-фрагменты оба слиты посредством пептида-коннектора с С- или N-концами тяжелых цепей, указанных в подпункте а); где пептидом-коннектором является (Gly-x-Ser)n, или (Gly-x-Ser)nGlym(х=3, n=3, 4, 5 или 6 и m=0,1, 2 или 3), или (х=4, n=2,3, или 5 и m=0, 1, 2 или 3) и где в Fab-фрагментах осуществлены следующие модификации: I) в обоих Fab-фрагментах, указанных в подпункте а), или в обоих Fab-фрагментах, указанных в подпункте б), вариабельные домены VL и VH заменены друг на друга и/или константные домены CL и СН1 замены друг на друга; II) в обоих Fab-фрагментах, указанных в подпункте а), вариабельные домены VL и VH заменены друг на друга и константные домены CL и СН1 заменены друг на друга, и в обоих Fab-фрагментах, указанных в подпункте б), вариабельные домены VL и VH заменены друг на друга или константные домены CL и СН1 заменены друг на друга; III) в обоих Fab-фрагментах, указанных в подпункте а), вариабельные домены VL и VH заменены друг на друга или константные домены CL и СН1 заменены друг на друга, и в обоих Fab-фрагментах, указанных в подпункте б), вариабельные домены VL и VH заменены друг на друга и константные домены CL и СН1 заменены друг на друга; IV) в обоих Fab-фрагментах, указанных в подпункте а), вариабельные домены VL и VH заменены друг на друга и в обоих Fab-фрагментах, указанных в подпункт</description><subject>BEER</subject><subject>BIOCHEMISTRY</subject><subject>CHEMISTRY</subject><subject>ENZYMOLOGY</subject><subject>FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE</subject><subject>METALLURGY</subject><subject>MICROBIOLOGY</subject><subject>MUTATION OR GENETIC ENGINEERING</subject><subject>ORGANIC CHEMISTRY</subject><subject>PEPTIDES</subject><subject>SPIRITS</subject><subject>VINEGAR</subject><subject>WINE</subject><fulltext>true</fulltext><rsrctype>patent</rsrctype><creationdate>2016</creationdate><recordtype>patent</recordtype><sourceid>EVB</sourceid><recordid>eNrjZFB28gwOcHX2dPN0VnD0C_F0d_XTdfL0c_H0c1cICPIPcfX0C-ZhYE1LzClO5YXS3AwKbq4hzh66qQX58anFBYnJqXmpJfFBoUam5saWhibORsZEKAEAHzwijQ</recordid><startdate>20160127</startdate><enddate>20160127</enddate><creator>VOL'FGANG SHEHFER</creator><creator>JURGEN MIKHAEHL' SHANTSER</creator><creator>JERG TOMAS REGULA</creator><creator>KRISTIAN KLAJN</creator><creator>ZABINE IMKHOF-JUNG</creator><scope>EVB</scope></search><sort><creationdate>20160127</creationdate><title>BISPECIFIC ANTIGEN-BINDING PROTEINS</title><author>VOL'FGANG SHEHFER ; JURGEN MIKHAEHL' SHANTSER ; JERG TOMAS REGULA ; KRISTIAN KLAJN ; ZABINE IMKHOF-JUNG</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-epo_espacenet_RU2573914C23</frbrgroupid><rsrctype>patents</rsrctype><prefilter>patents</prefilter><language>eng ; rus</language><creationdate>2016</creationdate><topic>BEER</topic><topic>BIOCHEMISTRY</topic><topic>CHEMISTRY</topic><topic>ENZYMOLOGY</topic><topic>FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE</topic><topic>METALLURGY</topic><topic>MICROBIOLOGY</topic><topic>MUTATION OR GENETIC ENGINEERING</topic><topic>ORGANIC CHEMISTRY</topic><topic>PEPTIDES</topic><topic>SPIRITS</topic><topic>VINEGAR</topic><topic>WINE</topic><toplevel>online_resources</toplevel><creatorcontrib>VOL'FGANG SHEHFER</creatorcontrib><creatorcontrib>JURGEN MIKHAEHL' SHANTSER</creatorcontrib><creatorcontrib>JERG TOMAS REGULA</creatorcontrib><creatorcontrib>KRISTIAN KLAJN</creatorcontrib><creatorcontrib>ZABINE IMKHOF-JUNG</creatorcontrib><collection>esp@cenet</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>VOL'FGANG SHEHFER</au><au>JURGEN MIKHAEHL' SHANTSER</au><au>JERG TOMAS REGULA</au><au>KRISTIAN KLAJN</au><au>ZABINE IMKHOF-JUNG</au><format>patent</format><genre>patent</genre><ristype>GEN</ristype><title>BISPECIFIC ANTIGEN-BINDING PROTEINS</title><date>2016-01-27</date><risdate>2016</risdate><abstract>FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to biotechnology and represents a method for producing a bispecific antigen-binding protein containing: two light chains and two heavy chains of a full-length antibody containing two Fab fragments and specifically binding to the first antigen; and two supplementary Fab fragments of the antibody, which specifically binds to the second antigen, wherein the above both supplementary Fab fragments are fused by means of a connector peptide to C- or N-terminals of the heavy chains specified in sub-clause a); wherein the connector peptide represents (Gly-x-Ser)n, or (Gly-x-Ser)nGlym(x = 3, n = 3, 4, 5 or 6 and m = 0, 1, 2 or 3), or (x = 4, n = 2, 3, or 5 and m = 0, 1, 2 or 3) and wherein the Fab fragments are modified as follows: I) in both of the Fab fragments specified in sub-clause a), or in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, and/or constant domains CL and CH1 are substituted by each other; II) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other, and constant domains CL and CH1 are substituted by each other, and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, or constant domains CL and CH1 are substituted by each other; III) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other, or constant domains CL and CH1 are substituted by each other, and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, and constant domains CL and CH1 are substituted by each other; IV) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other and in both of the Fab fragments specified in sub-clause b), constant domains CL and CH1 are substituted by each other; or V) in both of the Fab fragments specified in sub-clause a), constant domains CL and CH1 are substituted by each other and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other; whereas the method involves the stages of: a) transforming a host cell by means of expression vectors, which contain nucleic acid molecules coding the above bispecific antigen-binding protein; b) culturing the host cell in the environment, which enable synthesising a molecule of this bispecific antigen-binding protein; and c) recovering the molecule of the above bispecific antigen-binding protein from the above culture.EFFECT: invention enables producing the bispecific antibody having the structure described above.7 cl, 7 dwg, 3 tbl, 3 ex Изобретение относится к области биотехнологии и представляет собой способ получения биспецифического антигенсвязывающего белка, содержащего: две легкие цепи и две тяжелые цепи полноразмерного антитела, включающего два Fab-фрагмента и специфически связывающегося с первым антигеном; и два дополнительных Fab-фрагмента антитела, которое специфически связывается со вторым антигеном, где указанные дополнительные Fab-фрагменты оба слиты посредством пептида-коннектора с С- или N-концами тяжелых цепей, указанных в подпункте а); где пептидом-коннектором является (Gly-x-Ser)n, или (Gly-x-Ser)nGlym(х=3, n=3, 4, 5 или 6 и m=0,1, 2 или 3), или (х=4, n=2,3, или 5 и m=0, 1, 2 или 3) и где в Fab-фрагментах осуществлены следующие модификации: I) в обоих Fab-фрагментах, указанных в подпункте а), или в обоих Fab-фрагментах, указанных в подпункте б), вариабельные домены VL и VH заменены друг на друга и/или константные домены CL и СН1 замены друг на друга; II) в обоих Fab-фрагментах, указанных в подпункте а), вариабельные домены VL и VH заменены друг на друга и константные домены CL и СН1 заменены друг на друга, и в обоих Fab-фрагментах, указанных в подпункте б), вариабельные домены VL и VH заменены друг на друга или константные домены CL и СН1 заменены друг на друга; III) в обоих Fab-фрагментах, указанных в подпункте а), вариабельные домены VL и VH заменены друг на друга или константные домены CL и СН1 заменены друг на друга, и в обоих Fab-фрагментах, указанных в подпункте б), вариабельные домены VL и VH заменены друг на друга и константные домены CL и СН1 заменены друг на друга; IV) в обоих Fab-фрагментах, указанных в подпункте а), вариабельные домены VL и VH заменены друг на друга и в обоих Fab-фрагментах, указанных в подпункт</abstract><oa>free_for_read</oa></addata></record>
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subjects BEER
BIOCHEMISTRY
CHEMISTRY
ENZYMOLOGY
FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE
METALLURGY
MICROBIOLOGY
MUTATION OR GENETIC ENGINEERING
ORGANIC CHEMISTRY
PEPTIDES
SPIRITS
VINEGAR
WINE
title BISPECIFIC ANTIGEN-BINDING PROTEINS
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