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    Sequence asymmetric modified IgG4 bispecific antibodies
    3.
    发明授权
    Sequence asymmetric modified IgG4 bispecific antibodies 有权

    公开(公告)号：US09902768B2

    公开(公告)日：2018-02-27

    申请号：US14380310

    申请日：2013-02-22

    Applicant: UCB Pharma S.A.

    Inventor： David Paul Humphreys ,  Shirley Jane Peters

    IPC: C07K16/24 ,  C07K16/00 ,  C07K16/46

    CPC classification number: C07K16/24 ,  C07K16/00 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/51 ,  C07K2317/522 ,  C07K2317/53 ,  C07K2317/55 ,  C07K2317/94

    Abstract: The present disclosure provides an asymmetric mixed antibody comprising two heavy chains or heavy chain fragments each comprising at least a variable region, a hinge region and a CH1 domain, wherein a first heavy chain or fragment thereof is a class IgG4 and has: a the inter-chain cysteine at position 127, numbered according to the Kabat numbering system, in the CH1 domain is substituted with another amino acid; and b optionally one or more of the amino acids positioned in the upper hinge region is substituted with cysteine, and wherein the second heavy chain or fragment thereof is characterized in that part or all of the chain has a different amino acid sequence to said first heavy chain in at least the region outside the variable region (for example the constant region), formulations comprising the same, therapeutic used of both of the above, and processes for preparing the antibodies and formulation.

    Bacterial host strain
    5.
    发明授权
    Bacterial host strain 有权
    细菌宿主菌株

    公开(公告)号：US09550973B2

    公开(公告)日：2017-01-24

    申请号：US15083446

    申请日：2016-03-29

    Applicant: UCB PHARMA, S.A.

    Inventor： Mark Ellis ,  David Paul Humphreys

    IPC: C12P21/02 ,  C12N1/20 ,  C12R1/19 ,  C07K16/24 ,  C12N9/52 ,  C12N15/70

    CPC classification number: C12N1/20 ,  C07K16/241 ,  C07K16/244 ,  C07K2317/14 ,  C07K2317/20 ,  C07K2317/55 ,  C12N9/52 ,  C12N15/70 ,  C12P21/02 ,  C12R1/19 ,  Y02P20/52

    Abstract: A recombinant gram-negative bacterial cell comprising one or more of the following mutated protease genes: a) a mutated Tsp gene, wherein the mutated Tsp gene encodes a Tsp protein having reduced protease activity or is a knockout mutated Tsp gene; b) a mutated ptr gene, wherein the mutated ptr gene encodes a Protease III protein having reduced protease activity or is a knockout mutated ptr gene; and c) a mutated DegP gene encoding a DegP protein having chaperone activity and reduced protease activity; wherein the cell is isogenic to a wild-type bacterial cell except for the mutated Tsp gene and/or mutated ptr gene and/or mutated DegP gene and optionally a polynucleotide sequence encoding a protein of interest.

    Abstract translation: 包含一个或多个以下突变蛋白酶基因的重组革兰氏阴性细菌细胞：a）突变的Tsp基因，其中突变的Tsp基因编码具有降低的蛋白酶活性的Tsp蛋白或是敲除突变的Tsp基因; b）突变的ptr基因，其中突变的ptr基因编码具有降低的蛋白酶活性的蛋白酶III蛋白质或是敲除突变的ptr基因; 和c）编码具有伴侣活性和降低的蛋白酶活性的DegP蛋白的突变DegP基因; 其中所述细胞与野生型细菌细胞是同基因的，除了突变的Tsp基因和/或突变的ptr基因和/或突变的DegP基因和任选的编码目的蛋白质的多核苷酸序列。

    Sequence Symmetric Modified IgG4 Bispecific Antibodies
    6.
    发明申请
    Sequence Symmetric Modified IgG4 Bispecific Antibodies 审中-公开
    序列对称修饰的IgG4双特异性抗体

    公开(公告)号：US20150018529A1

    公开(公告)日：2015-01-15

    申请号：US14380309

    申请日：2013-02-22

    Applicant: UCB Pharma S.A.

    Inventor： David Paul Humphreys ,  Shirley Jane Peters

    IPC: C07K16/46

    CPC classification number: C07K16/468 ,  C07K16/00 ,  C07K2317/31 ,  C07K2317/51 ,  C07K2317/522 ,  C07K2317/53

    Abstract: The present disclosure relates to a symmetric bispecific antibody of the class IgG4 comprising two heavy chains which each comprise a variable domain, CH1 domain and a hinge region, wherein in each heavy chain: the cysteine in the CH1 domain which forms an inter-chain disulphide bond with a cysteine in a light chain is substituted with another amino acid; and optionally one or more of the amino acids positioned in the upper hinge region is substituted with cysteine, wherein the constant region sequence of each heavy chain is similar or identical and the variable region in each heavy chain is different, formulations comprising the same, the use of each of the above in treatment and processes for preparing said antibodies and formulations.

    Abstract translation: 本公开涉及类IgG4的对称双特异性抗体，其包含两个重链，每个重链各自包含可变结构域，CH1结构域和铰链区，其中在每个重链中：形成链间二硫键的CH1结构域中的半胱氨酸 与轻链中的半胱氨酸键合被另一个氨基酸取代; 并且任选地位于上部铰链区域中的一个或多个氨基酸被半胱氨酸取代，其中每个重链的恒定区序列相似或相同，并且每个重链中的可变区不同，包含其的制剂， 使用上述各项进行治疗和制备所述抗体和制剂的方法。

    Sequence Asymmetric Modified IgG4 Bispecific Antibodies
    7.
    发明申请
    Sequence Asymmetric Modified IgG4 Bispecific Antibodies 有权
    序列不对称修饰的IgG4双特异性抗体

    公开(公告)号：US20150017169A1

    公开(公告)日：2015-01-15

    申请号：US14380310

    申请日：2013-02-22

    Applicant: UCB Pharma S.A.

    Inventor： David Paul Humphreys ,  Shirley Jane Peters

    IPC: C07K16/24 ,  C07K16/46

    CPC classification number: C07K16/24 ,  C07K16/00 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/51 ,  C07K2317/522 ,  C07K2317/53 ,  C07K2317/55 ,  C07K2317/94

    Abstract: The present disclosure provides an asymmetric mixed antibody comprising two heavy chains or heavy chain fragments each comprising at least a variable region, a hinge region and a CH1 domain, wherein a first heavy chain or fragment thereof is a class IgG4 and has: a the inter-chain cysteine at position 127, numbered according to the Kabat numbering system, in the CH1 domain is substituted with another amino acid; and b optionally one or more of the amino acids positioned in the upper hinge region is substituted with cysteine, and wherein the second heavy chain or fragment thereof is characterised in that part or all of the chain has a different amino acid sequence to said first heavy chain in at least the region outside the variable region (for example the constant region), formulations comprising the same, therapeutic used of both of the above, and processes for preparing the antibodies and formulation.

    Abstract translation: 本公开提供了包含两个重链或重链片段的不对称混合抗体，其各自包含至少一个可变区，铰链区和CH1结构域，其中第一重链或其片段是IgG4类，并且具有： 在CH1结构域中根据Kabat编号系统编号的位置127处的链半胱氨酸被另一个氨基酸取代; 并且b任选地一个或多个位于上部铰链区域的氨基酸被半胱氨酸取代，并且其中第二重链或其片段的特征在于部分或全部链具有与所述第一重质 至少在可变区域外的区域（例如，恒定区域），包含上述两者的治疗剂，以及用于制备抗体和制剂的方法。

    ALBUMIN BINDING ANTIBODIES AND BINDING FRAGMENTS THEREOF
    8.
    发明申请
    ALBUMIN BINDING ANTIBODIES AND BINDING FRAGMENTS THEREOF 有权
    ALBUMIN BINDING抗体及其结合片段

    公开(公告)号：US20140302033A1

    公开(公告)日：2014-10-09

    申请号：US14356181

    申请日：2012-11-09

    Applicant: UCB PHARMA S.A.

    Inventor： Ralph Adams ,  Pavalli Bhatta ,  Sam Phillip Heywood ,  David Paul Humphreys

    IPC: C07K16/18

    CPC classification number: C07K16/18 ,  C07K16/2878 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/624 ,  C07K2317/92

    Abstract: A serum albumin binding antibody or fragment thereof comprising a heavy chain variable domain having the sequence given in SEQ ID NO: 1 or SEQ ID NO:2 and/or comprising a light chain variable domain having the sequence given in SEQ ID NO:3 or SEQ ID NO:4, in particular comprising a heavy chain variable domain and a light chain variable domain having the sequence given in SEQ ID NO: 1 and SEQ ID NO:3 or a heavy chain variable domain and a light chain variable domain having the sequence given in SEQ ID NO: 2 and SEQ ID NO:4. The disclosure also extends to polynucleotides encoding the antibodies or fragments, vectors comprising same and host cells capable of expressing the polynucleotides. The disclosure further includes pharmaceutical compositions comprising the antibodies or fragments and therapeutic used of any one of the same.

    Abstract translation: 1.一种血清白蛋白结合抗体或其片段，其包含具有SEQ ID NO：1或SEQ ID NO：2中给出的序列的重链可变结构域和/或包含具有SEQ ID NO：3中给出的序列的轻链可变区或 SEQ ID NO：4，特别包括具有SEQ ID NO：1和SEQ ID NO：3中给出的序列的重链可变结构域和轻链可变区或重链可变结构域和具有 SEQ ID NO：2和SEQ ID NO：4中给出的序列。 本公开还延伸到编码抗体或片段的多核苷酸，包含其的载体和能够表达多核苷酸的宿主细胞。 本公开还包括药物组合物，其包含使用其中任何一种的抗体或片段和治疗剂。

    Bacterial host strain comprising a mutant spr gene and having reduced Tsp activity
    10.
    发明授权
    Bacterial host strain comprising a mutant spr gene and having reduced Tsp activity 有权
    细菌宿主菌株包含突变体spr基因并具有降低的Tsp活性

    公开(公告)号：US09587227B2

    公开(公告)日：2017-03-07

    申请号：US14600089

    申请日：2015-01-20

    Applicant: UCB PHARMA, S.A.

    Inventor： Mark Ellis ,  David Paul Humphreys

    IPC: C12N9/04 ,  C07K14/245 ,  C12N9/52 ,  C12N15/70

    CPC classification number: C12N9/0006 ,  C07K14/245 ,  C12N9/52 ,  C12N15/70 ,  C12Y101/01

    Abstract: The present invention provides a recombinant gram-negative bacterial cell comprising a mutant spr gene encoding a spr protein having a mutation at one or more amino acids selected from D133, H145, H157, N31, R62, 170, Q73, C94, S95, V98, Q99, R100, L108, Y115, V135, L136, G140, R144 and G147 and wherein the cell has reduced Tsp protein activity compared to a wild-type cell.

    Abstract translation: 本发明提供了一种重组革兰氏阴性细菌细胞，其包含编码在选自D133，H145，H157，N31，R62,170，Q73，C94，S95，V98中的一个或多个氨基酸具有突变的spr蛋白的突变型spr基因 ，Q99，R100，L108，Y115，V135，L136，G140，R144和G147，并且其中与野生型细胞相比，细胞具有降低的Tsp蛋白活性。

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