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1. 发明授权

US11780919B2 Bispecific antigen binding molecules targeting OX40 and FAP 有权
公开(公告)号：US11780919B2
公开(公告)日：2023-10-10
申请号：US17218948
申请日：2021-03-31
申请人： Hoffmann-La Roche Inc.
发明人： Maria Amann , Juergen Peter Bachl , Alexander Bujotzek , Carina Cantrill , Harald Duerr , Janine Faigle , Sabine Imhof-Jung , Christian Klein , Thomas Kraft , Estelle Marrer-Berger , Ekkehard Moessner , Laurene Pousse , Petra Rueger , Johannes Sam , Roland Staack , Dietrich Tuerck , Pablo Umana , Joerg Zielonka
IPC分类号： A61K39/00 , C07K16/28 , A61P35/00 , A61K45/06 , C07K16/30 , C07K16/46
CPC分类号： C07K16/2809 , A61K45/06 , A61P35/00 , C07K16/2878 , C07K16/30 , C07K16/468 , A61K2039/505 , C07K2317/565 , C07K2317/622
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.

2. 发明申请

US20210364504A1 METHOD FOR DETERMINING THE AMOUNT OF A THERAPEUTIC ANTIBODY IN THE BRAIN 有权
公开(公告)号：US20210364504A1
公开(公告)日：2021-11-25
申请号：US17136289
申请日：2020-12-29
申请人： Hoffmann-La Roche Inc.
发明人： Martin Schaefer , Sylvia Rottach , Gregor Jordan , Kay-Gunnar Stubenrauch , Roland Staack , Kevin Brady
IPC分类号： G01N33/543 , C07K16/28 , C07K16/40
摘要： Herein is reported a method for determining the concentration of a therapeutic antibody in a tissue of an experimental animal to whom the therapeutic antibody had been administered, wherein the interference from residual blood in a tissue sample of the experimental animal, which is used for determining the concentration of the therapeutic antibody in said tissue, is reduced, wherein the concentration of the therapeutic antibody in the tissue of the experimental animal is calculated with the following formula: C tmAb , tissue = C tmAb , tissue , det . C tissue , sample - C refmAb , tissue , det . C tissue , sample C refmAb , plasma . det . * C tmAb , plasma , det . wherein CtmAb,tissue,det.=obtained by determining the concentration of the therapeutic antibody in the tissue sample of the experimental animal, CtmAb,plasma,det.=obtained by determining the concentration of the therapeutic antibody in a blood sample of the experimental animal directly prior to taking the tissue sample, CrefmAb,tissue,det.=obtained by determining the concentration of the inert reference antibody in the tissue sample of the experimental animal, CrefmAb,plasma,det.=obtained by determining the concentration of an inert reference antibody in the blood sample of the experimental animal directly prior to taking the tissue sample, Ctissue,sample=obtained by determining the tissue concentration in the tissue sample, whereby the inert reference antibody does not penetrate into said tissue, whereby the inert reference antibody is administered 2 to 10 minutes prior to obtaining the tissue and blood sample.

3. 发明授权

US11913945B2 Method for determining the amount of a therapeutic antibody in the brain 有权
公开(公告)号：US11913945B2
公开(公告)日：2024-02-27
申请号：US17136289
申请日：2020-12-29
申请人： Hoffmann-La Roche Inc.
发明人： Martin Schaefer , Sylvia Rottach , Gregor Jordan , Kay-Gunnar Stubenrauch , Roland Staack , Kevin Brady
IPC分类号： G01N33/543 , C07K16/28 , C07K16/40 , G01N33/68
CPC分类号： G01N33/543 , C07K16/2803 , C07K16/2881 , C07K16/2887 , C07K16/40 , G01N33/54306 , G01N33/6854 , C07K2317/31 , G01N2800/52
摘要： Herein is reported a method for determining the concentration of a therapeutic antibody in a tissue of an experimental animal to whom the therapeutic antibody had been administered, wherein the interference from residual blood in a tissue sample of the experimental animal, which is used for determining the concentration of the therapeutic antibody in said tissue, is reduced by applying an inert reference antibody that does not penetrate into said tissue, whereby the inert reference antibody is administered 2 to 10 minutes prior to obtaining the tissue and blood sample.

4. 发明授权

US11892448B2 Immunoassay-based determination of in-solution binding kinetics 有权
公开(公告)号：US11892448B2
公开(公告)日：2024-02-06
申请号：US16508254
申请日：2019-07-10
申请人： Hoffmann-La Roche Inc.
发明人： Uwe Dahl , Gregor Jordan , Roland Staack
IPC分类号： G01N31/00 , G01N33/53 , G01N33/557 , G01N33/15
CPC分类号： G01N33/557 , G01N33/15
摘要： Herein is reported a method for the determination of the binding affinity of a binder and its ligand comprising the step of determining based on the result of an immunoassay the fraction of free binder in a sample comprising binder, ligand and binder-ligand-complexes for at least two different binder:ligand ratios in the sample, and if the determined fraction of free binder is not comparable for all used binder:ligand ratios then the binder:ligand ratio in the sample is lowered and the sample is re-analyzed by the same immunoassay, and calculating based on the fraction of free binder in the previous step the binding affinity for the binder to its ligand.

5. 发明授权

US10458981B2 Three-step acid dissociation enzyme linked immunosorbent (TADELIS) assay 有权
公开(公告)号：US10458981B2
公开(公告)日：2019-10-29
申请号：US16009369
申请日：2018-06-15
申请人： Hoffmann-La Roche Inc.
发明人： Gregor Jordan , Roland Staack
IPC分类号： G01N31/00 , G01N33/53 , G01N33/543 , G01N33/536 , G01N33/68 , G01N33/94 , G01N33/58
摘要： Herein is reported a method for determining in a sample the (total, i.e. binding competent) amount of a ligand of a ligand-binding protein (therapeutic) comprising the following steps in the following order: subjecting the sample to an acid treatment, forming in solution a non-covalent complex comprising i) an anti-ligand antibody, ii) the ligand, and iii) labelled ligand-binding protein, by adding anti-ligand antibody and labelled ligand-binding protein to the sample, and determining the amount of the complex and thereby determining the amount of the ligand of the ligand-binding protein.

6. 发明授权

US09797900B2 Multiplexed chromatography-immunoassay method for the characterization of circulating immune complexes 有权
公开(公告)号：US09797900B2
公开(公告)日：2017-10-24
申请号：US14478536
申请日：2014-09-05
申请人： Hoffmann-La Roche Inc.
发明人： Uwe Dahl , Gregor Jordan , Roland Staack
IPC分类号： G01N31/00 , G01N33/53 , G01N33/564 , G01N33/68 , G01N33/94
CPC分类号： G01N33/564 , G01N33/686 , G01N33/94
摘要： Thus, herein is reported a method for analyzing/characterizing circulating immune complexes (CICs) formed in vivo comprising a size-exclusion chromatography of a sample obtained from a mammal to which the drug had been administered at least once for determining the weight/size of the immune complexes, optionally a second non-SEC chromatography, and at least one immunoassay, whereby the immune complex is characterized by the correlation of the immune complex size and the immunoassay result/read-out. Also reported herein is the use of a method as reported herein for determining a correlation to altered pharmacokinetics, for determining loss or reduction of efficacy, for determining neutralization of natural counterparts of the drug, for determining immune and hypersensitivity reactions, including serum sickness/type III hypersensitivity reaction/immune complex-mediated disease.

7. 发明申请

US20150168396A1 IMMUNOASSAY-BASED DETERMINATION OF IN-SOLUTION BINDING KINETICS 审中-公开
标题翻译：基于免疫测定的解决方案的绑定动力学
公开(公告)号：US20150168396A1
公开(公告)日：2015-06-18
申请号：US14419984
申请日：2013-08-02
申请人： Hoffmann-La Roche Inc.
发明人： Uwe Dahl , Gregor Jordan , Roland Staack
IPC分类号： G01N33/557 , G01N33/15
摘要： Herein is reported a method for the determination of the binding affinity of a binder and its ligand comprising the step of determining based on the result of an immunoassay the fraction of free binder in a sample comprising binder, ligand and binder-ligand-complexes for at least two different binder:ligand ratios in the sample, and if the determined fraction of free binder is not comparable for all used binder:ligand ratios then the binder:ligand ratio in the sample is lowered and the sample is re-analyzed by the same immunoassay, and calculating based on the fraction of free binder in the previous step the binding affinity for the binder to its ligand.
摘要翻译：本文报道了用于测定粘合剂及其配体的结合亲和力的方法，包括基于免疫测定结果确定样品中游离粘合剂部分的步骤的步骤，所述样品包含粘合剂，配体和粘合剂 - 配体 - 复合物样品中至少两种不同的粘合剂：配体比例，如果游离粘合剂的确定部分对于所有使用的粘合剂：配体比例是不可比的，则样品中的粘合剂：配体比率降低，并且将样品重新分析免疫测定，并且基于前一步骤中游离粘合剂的分数来计算粘合剂对其配体的结合亲和力。

8. 发明公开

US20240219381A1 METHOD FOR DETERMINING THE AMOUNT OF A THERAPEUTIC ANTIBODY IN THE BRAIN 审中-公开
公开(公告)号：US20240219381A1
公开(公告)日：2024-07-04
申请号：US18430887
申请日：2024-02-02
申请人： Hoffmann-La Roche Inc.
发明人： Martin Schaefer , Sylvia Rottach , Gregor Jordan , Kay-Gunnar Stubenrauch , Roland Staack , Kevin Brady
IPC分类号： G01N33/543 , C07K16/28 , C07K16/40 , G01N33/68
CPC分类号： G01N33/543 , C07K16/2803 , C07K16/2881 , C07K16/2887 , C07K16/40 , G01N33/54306 , G01N33/6854 , C07K2317/31 , G01N2800/52
摘要： Herein is reported a method for determining the concentration of a therapeutic antibody in a tissue of an experimental animal to whom the therapeutic antibody had been administered, wherein the interference from residual blood in a tissue sample of the experimental animal, which is used for determining the concentration of the therapeutic antibody in said tissue, is reduced, wherein the concentration of the therapeutic antibody in the tissue of the experimental animal is calculated with the following formula:

C

tmAb
,

t
⁢
i
⁢
s
⁢
s
⁢
u
⁢
e

=

C

t
⁢
mAb

,
tissue
,

det
.

C

tissue
,
sample

-

C

refmAb
,
tissue
,

det
.

C

tissue
,
sample

C

refmAb
,
plasma
,

det
.

*

C

tmAb
,
plasma
,

det
.

wherein CtmAb,tissue,det.=obtained by determining the concentration of the therapeutic antibody in the tissue sample of the experimental animal, CtmAb,plasma,det.=obtained by determining the concentration of the therapeutic antibody in a blood sample of the experimental animal directly prior to taking the tissue sample, CrefmAb,tissue,det.=obtained by determining the concentration of the inert reference antibody in the tissue sample of the experimental animal, CrefmAb,plasma,det.=obtained by determining the concentration of an inert reference antibody in the blood sample of the experimental animal directly prior to taking the tissue sample, Ctissue,sample=obtained by determining the tissue concentration in the tissue sample, whereby the inert reference antibody does not penetrate into said tissue, whereby the inert reference antibody is administered 2 to 10 minutes prior to obtaining the tissue and blood sample.

9. 发明申请

US20200300852A1 TARGET INTERFERENCE SUPPRESSED ANTI-DRUG ANTIBODY ASSAY 审中-公开
公开(公告)号：US20200300852A1
公开(公告)日：2020-09-24
申请号：US16763435
申请日：2018-11-27
申请人： Hoffmann-La Roche Inc.
发明人： Uwe Dahl , Gregor Jordan , Roland Staack , Miriam Moheysen-Zadeh
IPC分类号： G01N33/543
摘要： Herein is reported an immunoassay for quantifying the amount of anti-drug antibody, which anti-drug antibody can specifically bind to a drug antibody, which drug antibody can specifically bind to a therapeutic target, in a serum or plasma sample comprising the steps of a) incubating the serum or plasma sample at a pH value that is about the pI value of the target, and optionally removing formed precipitate after the incubation, b) incubating the serum or plasma sample obtained in step a) at a pH value of about 2, and optionally centrifuging the incubated sample to remove formed precipitate, c) adjusting the pH value to about 7.4, adding capture antibody conjugated to a first member of a binding pair and tracer antibody conjugated to a detectable label to the serum or plasma sample obtained in step b) and incubating the mixture to form a capture antibody-anti-drug antibody-tracer antibody-complex, d) quantifying the complex formed in step c) and thereby quantifying the amount of anti-drug antibody in the serum or plasma sample.

10. 发明申请

US20200173989A1 IMMUNOASSAY-BASED DETERMINATION OF IN-SOLUTION BINDING KINETICS 审中-公开
公开(公告)号：US20200173989A1
公开(公告)日：2020-06-04
申请号：US16508254
申请日：2019-07-10
申请人： Hoffmann-La Roche Inc.
发明人： Uwe Dahl , Gregor Jordan , Roland Staack
IPC分类号： G01N33/557 , G01N33/15
摘要： Herein is reported a method for the determination of the binding affinity of a binder and its ligand comprising the step of determining based on the result of an immunoassay the fraction of free binder in a sample comprising binder, ligand and binder-ligand-complexes for at least two different binder:ligand ratios in the sample, and if the determined fraction of free binder is not comparable for all used binder:ligand ratios then the binder:ligand ratio in the sample is lowered and the sample is re-analyzed by the same immunoassay, and calculating based on the fraction of free binder in the previous step the binding affinity for the binder to its ligand.

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