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1. 发明申请

WO2022129120A1 ANTI-HLA-G ANTIBODIES AND USE THEREOF 审中-公开
公开(公告)号：WO2022129120A1
公开(公告)日：2022-06-23
申请号：PCT/EP2021/085810
申请日：2021-12-15
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： BUJOTZEK, Alexander , CARPY GUTIERREZ CIRLOS, Alejandro , FREIMOSER-GRUNDSCHOBER, Anne , HAGE, Carina , HOFER, Thomas , KIRCHNER, Silke , MAJETY, Meher , MOESSNER, Ekkehard , NEUMANN, Christiane , SPICK, Christian , TIEFENTHALER, Georg , WEINDL, Thomas
IPC分类号： C07K16/28 , A61P35/00 , A61P37/02 , A61K39/00
摘要： The present invention relates antibodies that bind to human HLA- G, multispecific antibodies thereof, their preparation, formulations and methods of using the same. In particular, specific variants of the antibody designated HLA-G-0090 are provided with mutations in the CDR1 of the variable region of the light chain (CDR-L1) which comprises a potential glycosylation site (NSS). Two particular variants showed improved binding properties, good expressability and stability, while showing no more N-glycosylation at the CDR-L1 of the light chain (so no Fab glycosylation could be detected). In one embodiment bispecific antibodies are disclosed comprising the variants for the HLA-G antibody and an antibody binding human CD3.

2. 发明申请

WO2019202041A1 MULTISPECIFIC ANTIBODIES AND USE THEREOF 审中-公开
公开(公告)号：WO2019202041A1
公开(公告)日：2019-10-24
申请号：PCT/EP2019/060008
申请日：2019-04-17
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： DENGL, Stefan , FENN, Sebastian , FISCHER, Jens , KIRSTENPFAD, Claudia , KLOSTERMANN, Stefan , MOELLEKEN, Joerg , TIEFENTHALER, Georg , BUJOTZEK, Alexander , MAJETY, Meher , KIRCHNER, Silke
IPC分类号： C07K16/28
摘要： The present invention relates to multispecific antibodies that bind to HLA-G ant to a T cell activating antigen, their preparation, formulations and methods of using the same.

3. 发明申请

WO2022129313A1 PRECURSOR PROTEINS AND KIT FOR TARGETED THERAPY 审中-公开
公开(公告)号：WO2022129313A1
公开(公告)日：2022-06-23
申请号：PCT/EP2021/086151
申请日：2021-12-16
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： BRINKMANN, Ulrich , BUJOTZEK, Alexander , BULDUN, Can , GEORGES, Guy
IPC分类号： C07K16/00 , C07K16/46 , A61K38/19 , A61K38/20 , C07K14/54 , C07K14/52 , C07K14/55
摘要： The present invention relates to a set of precursor proteins comprising an inactivated receptor ligand or enzyme and methods for their use in therapy.

4. 发明申请

WO2021198333A1 BISPECIFIC ANTIGEN BINDING MOLECULES TARGETING OX40 AND FAP 审中-公开
公开(公告)号：WO2021198333A1
公开(公告)日：2021-10-07
申请号：PCT/EP2021/058435
申请日：2021-03-31
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： AMANN, Maria , BACHL, Juergen Peter , BUJOTZEK, Alexander , CANTRILL, Carina , DUERR, Harald , FAIGLE, Janine , IMHOF-JUNG, Sabine , KLEIN, Christian , KRAFT, Thomas , MARRER-BERGER, Estelle , MOESSNER, Ekkehard , POUSSE, Laurene , RUEGER, Petra , SAM, Johannes , STAACK, Roland , TUERCK, Dietrich , UMAÑA, Pablo , ZIELONKA, Joerg
IPC分类号： A61K39/395 , C07K16/28 , C07K16/40 , A61K38/17 , C07K16/2878 , C07K16/4283 , C07K2317/31 , C07K2317/34 , C07K2317/35 , C07K2317/522 , C07K2317/55 , C07K2317/64 , C07K2317/66 , C07K2317/94
摘要： The invention relates to novel bispecific antigen binding molecules, comprising at least two antigen binding domains capable of specific binding to OX40 and a particular antigen binding domain capable of specific binding to Fibroblast Activation Protein (FAP), and to methods of producing these molecules and to methods of using the same.

5. 发明申请

WO2021123173A1 IL-37 FUSION PROTEINS AND USES THEREOF 审中-公开
公开(公告)号：WO2021123173A1
公开(公告)日：2021-06-24
申请号：PCT/EP2020/087031
申请日：2020-12-18
申请人： F. HOFFMANN-LA ROCHE AG , MONASH UNIVERSITY , HOFFMANN-LA ROCHE INC
发明人： TIEFENTHALER, Georg , BUJOTZEK, Alexander , LARIVIERE, Laurent , SCHUMACHER, Felix , ELLISDON, Andrew , NOLD, Claudia , NOLD, Marcel , WHISSTOCK, James
IPC分类号： C07K14/54 , C12N15/62 , A61K38/20 , A61K38/00 , C07K2319/30
摘要： The present invention relates to polypeptides, particularly fusion protein variants comprising interleukin-37 (IL-37) and related therapeutics and compositions thereof. More particularly, the invention relates to fusion proteins comprising a mutant IL-37 polypeptide and an Fc region of an antibody. The biophysical stability such as thermal stability of said fusion proteins can be improved compared to a reference IL-37 construct, such as a wild-type IL-37 polypeptide or a mutant variant of an IL-37 polypeptide. It also relates to the fusion polypeptide variants and compositions for use in treating inflammatory diseases or conditions. In addition, the present invention relates to nucleic acid molecules encoding such fusion proteins, and vectors and host cells comprising such nucleic acid molecules.

6. 发明申请

WO2020200944A1 METHOD FOR GENERATING AVID-BINDING MULTISPECIFIC ANTIBODIES 审中-公开
公开(公告)号：WO2020200944A1
公开(公告)日：2020-10-08
申请号：PCT/EP2020/058271
申请日：2020-03-25
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： BRINKMANN, Ulrich , BUJOTZEK, Alexander , GEORGES, Guy , SCHRADE, Anja
IPC分类号： C07K16/00 , C07K16/28 , C07K16/32
摘要： Herein is reported a method for increasing the (avid-)binding specificity of a bispecific antibody comprising a first mammalian or mammalianized binding site specifically binding to a first (cell-surface) antigen and a second binding site specifically binding to a second (cell-surface) antigen, wherein the first mammalian or mammalianized binding site is at least a pair of an immunoglobulin light chain variable domain and immunoglobulin heavy chain variable domain, by decreasing the binding affinity of the mammalian or mammalianized binding site to its antigen by mutating in the first mammalian or mammalianized binding site at least one amino acid residue at a position in the CDRs of the light chain variable domain or in the CDR1 or CDR2 of the heavy chain variable domain or in the two framework positions directly preceding the CDR3 in the heavy chain variable domain to an amino acid residue present at said position in a germline immunoglobulin amino acid sequence of the same mammalian species as that of the mammalian or mammalianized binding site.

7. 发明申请

WO2018162376A1 METHOD FOR DISCOVERY OF ALTERNATIVE ANTIGEN SPECIFIC ANTIBODY VARIANTS 审中-公开
公开(公告)号：WO2018162376A1
公开(公告)日：2018-09-13
申请号：PCT/EP2018/055278
申请日：2018-03-05
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： GEORGES, Guy , KLOSTERMANN, Stefan , TISSOT, Alain , ROS, Francesca , BUJOTZEK, Alexander , WRZODEK, Clemens , SCHULTZ, Frederic
IPC分类号： C12N15/10 , C40B30/02 , G06F19/22 , C12Q1/6811
摘要： Herein is reported a method for selecting a variant of a parental antibody variable domain encoding nucleic acid, wherein the parental antibody variable domain amino acid sequence encoded by said encoding nucleic acid has at least one developability hot spot, the method comprising the steps of (i) providing a multitude of DNA-containing samples (genomic material of antibody secreting B- cell) each including one or more antibody variable domain encoding nucleic acids; (ii) performing PCR amplification of said antibody variable domain encoding nucleic acids of (i) using consensus sequence-specific primers to obtain amplification products (wherein said consensus sequence-specific primers bind to consensus sequences that are common to a plurality of genes within the genetic loci set, thereby generating a pool of amplification products); (iii) sequencing a plurality of said amplification products obtained in step (ii) in order to determine the relative proportion of each nucleotide at each position in a sequencing read; (iv) performing a sequence alignment between the sequencing read results of (iii) and the parental antibody variable domain encoding nucleic acid; (v) performing a sequence-identity/homology-based ranking of the antibody variable domain encoding nucleic acids in said sequence alignment with the parental antibody variable domain encoding nucleic acid being the perfect/template/reference sequence; and (vi) selecting the variant antibody variable domain encoding nucleic acid based on the sequence ranking of step (v), whereby the variant selected in step (vi) is selected so that the developability hot-spot is removed.

8. 发明申请

WO2019154890A1 ANTIBODIES BINDING TO GPRC5D 审中-公开
公开(公告)号：WO2019154890A1
公开(公告)日：2019-08-15
申请号：PCT/EP2019/052962
申请日：2019-02-07
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： FERTIG, Georg , KLEIN, Christian , LORENZ, Stefan , XU, Wei , BERNASCONI, Marie-Luise , BUJOTZEK, Alexander
IPC分类号： C07K16/28 , A61K39/00 , A61P35/00
摘要： The present invention generally relates to antibodies that bind to GPRC5D, including bispecific antigen binding molecules e.g. for activating T cells. In addition, the present invention relates to polynucleotides encoding such antibodies, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the antibodies, and to methods of using them in the treatment of disease.

9. 发明申请

WO2019122052A3 ANTIBODIES BINDING TO HLA-A2/WT1 审中-公开
公开(公告)号：WO2019122052A3
公开(公告)日：2019-06-27
申请号：PCT/EP2018/086055
申请日：2018-12-20
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： BENZ, Joerg , KLEIN, Christian , KLOSTERMANN, Stefan , MOESSNER, Ekkehard , SAM, Johannes , UMANA, Pablo , HANISCH, Lydia, Jasmin , BUJOTZEK, Alexander , XU, Wei
IPC分类号： C07K16/28 , A61K39/00 , A61P35/00
摘要： The present invention generally relates to antibodies that bind to HLA-A2/WT1, including bispecific antigen binding molecules e.g. for activating T cells. In addition, the present invention relates to polynucleotides encoding such antibodies, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the antibodies, and to methods of using them in the treatment of disease.

10. 发明申请

WO2016062734A1 VH-VL-INTERDOMAIN ANGLE BASED ANTIBODY HUMANIZATION 审中-公开
标题翻译：基于VH-VL-间质角的抗体人源化
公开(公告)号：WO2016062734A1
公开(公告)日：2016-04-28
申请号：PCT/EP2015/074294
申请日：2015-10-21
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： BUJOTZEK, Alexander , GEORGES, Guy , LIPSMEIER, Florian
IPC分类号： C07K16/00
CPC分类号： C07K16/2803 , C07K16/2896 , C07K16/40 , C07K2317/24 , C07K2317/56 , C07K2317/92 , C12Y304/21106
摘要： Herein is reported a method for selecting one or more variant antibody Fv fragments derived from a parent antibody Fv fragment comprising the steps of i) generating a multitude of variant antibody Fv fragments by grafting/transferring one or more specificity determining residues from the parent antibody Fv fragment on an acceptor antibody Fv fragment, whereby each variant antibody Fv fragment of the multitude of variant antibody Fv fragments differs from the other variant antibody Fv fragments by at least one amino acid residue, ii) determining the VH- VL-orientation for the parent Fv fragment and for each of the variant antibody Fv fragments of the multitude of variant antibody Fv fragments based on a sequence fingerprint of the antibody Fv fragment, and iii) selecting those variant antibody Fv fragments that have the smallest difference in the VH-VL-orientation compared to the parent antibody's VH-VL-orientation and thereby selecting one or more variant antibody Fv fragments derived from a parent antibody Fv fragment, whereby the one or more variant antibody Fv fragments bind to the same antigen as the parent antibody Fv fragment.
摘要翻译：本文报道了用于选择衍生自亲本抗体Fv片段的一种或多种变体抗体Fv片段的方法，其包括以下步骤：i）通过从母体抗体Fv接枝/转移一种或多种特异性确定残基而产生多种变体抗体Fv片段受体抗体Fv片段的片段，其中多个变体抗体Fv片段的每个变体抗体Fv片段与其他变体抗体Fv片段与至少一个氨基酸残基不同，ii）确定母体的VH- VL-取向 Fv片段和基于抗体Fv片段的序列指纹图谱的多种变体抗体Fv片段的每个变体抗体Fv片段，以及iii）选择在VH-VL-片段中具有最小差异的那些变体抗体Fv片段，方向与亲本抗体的VH-VL取向相比较，从而选择一种或多种衍生的变体抗体Fv片段来自亲本抗体Fv片段，由此一个或多个变体抗体Fv片段与亲本抗体Fv片段结合相同的抗原。

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