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Humanized antibodies against TL1A

A humanized antibody, CDR-L1 technology, applied in the direction of antibodies, anti-animal/human immunoglobulins, anti-inflammatory agents, etc., can solve the problems of recurrence of tuberculosis infection, worsening of heart failure, and increased incidence of lymphoma

Active Publication Date: 2010-12-01
TEVA BIOPHARM USA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although infliximab is highly specific and generally well tolerated, infliximab can lead to relapse of tuberculosis infection and worsening of heart failure, demyelinating disease and increased incidence of lymphoma

Method used

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  • Humanized antibodies against TL1A
  • Humanized antibodies against TL1A
  • Humanized antibodies against TL1A

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] The amino acid sequences of the VH and VK regions of mouse and hamster anti-TL1A monoclonal antibodies prepared as described herein are shown below. The CDR regions of the variable domains are underlined.

[0113] 12D08VK:

[0114] DVLMTQTPLS LPVSLGDQAS ISCRSSQSIV HSNGNTYLDW YLQKPGQSPN LLIYKVSNRF

[0115] SGVPDRFSGS GSGTDFTLKI SRVEAEDLGV YYCFQGSHVP LTFGAGTKLE LKR

[0116] 16H02VK:

[0117] DVLMTQTPLS LPVSLGDQAS ISCKSSQNIV HSDGNTYLEW YLQKPGQSPK LLIYKVSNRF

[0118] SGVPDRFSGS GSGTDFTLKI SRVEAEDLGV YYCFQGSHVP LTFGSGTKLE IKR

[0119] 15E09VK:

[0120] ETTVTQSPAS LSMAIGEKVT IRCITSTDID DDMNWYQQKP GEPPKLLISE GNTLRPGVPS

[0121] RFSSSSGYGTD FVFTIENMLS EDVADYYCLQ SDNLPLTFGA GTKLELKR

[0122] 19E06VK:

[0123] DIVMTQSPSS LAVSTGGTVT LTCLSSQSLF SSDTNKNYLN WYLQKPGQSP KLLVYHASTR

[0124] LTGVPDRFIG SGSGTDFTLT INSVQAEDLG DYYCQQHFRP PFTFGRGTKL EIKR

[0125] IB4VK AA

[0126] QIVLTQSPAIMSASLGAEITLTC SASSSVNYMH WYQQRSGTSPKLLIY STSNLAS GVPSRFSGS

[0127] GSGTFYSLTISSVEAEDAAD...

Embodiment 2

[0170] This example describes an assay protocol for measuring inhibition of TL1A-induced caspase activity on TF-1 cells.

[0171] To determine the neutralizing activity of anti-TL1A antibodies, their effect on TL1A-induced caspase activity in TF-1 cells was determined. See figure 1 . In RPMI medium containing 1% fetal bovine serum, TF-1 cells were seeded at 75000 cells / well in a black 96-well plate with a transparent bottom. Cells were treated with 10 μg / mL cyclohexamide and 100 ng / mL TL1A for 6 hours at 37°C in the absence or presence of various concentrations of mouse or hamster parental TL1A antibody. Caspase activity was measured by Apo-One homogeneous caspase-3 / 7 assay kit (Promega). An equal volume of Apo-One Homogenous Caspase-3 / 7 Assay Buffer containing the caspase substrate (Z-DEVD-Rhodamine) was added to each well containing cells. After overnight incubation, fluorescence was measured by a Wallac Victor2 fluorescence analyzer with an excitation filter of 485 nm ...

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Abstract

Disclosed are humanized antibodies that bind specifically to TNF superfamily member 15 (TNFSF 15), also known as TLlA. Methods of making and using the anti-TLl A antibodies are also described. The humanized antibodies may be antagonists and may used to treat or diagnose conditions associated with TLlA function.

Description

[0001] This application claims the benefit of priority to US Provisional Patent Application Serial No. 60 / 987,651, filed November 13,2007. The content of this provisional application is hereby incorporated by reference in its entirety. technical field [0002] The present invention relates to antibodies against TL1A, and methods of making and using such antibodies. Such antibodies are expected to be particularly useful in the treatment of inflammatory diseases such as Crohn's disease. Background technique [0003] Proteins structurally related to tumor necrosis factor (TNF) are collectively referred to as the TNF superfamily. TL1A, a member of the TNF superfamily, is a TNF-like cytokine that binds to death domain receptor (DR) 3 and provides co-stimulatory signals to activated lymphocytes. Through this interaction, TL1A induces the secretion of IFN-γ and thus may be involved in the formation of T helper-1 type effector responses. [0004] TL1A is a type II transmembrane p...

Claims

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Application Information

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IPC IPC(8): C07K16/28A61K39/395A61P37/06A61P35/00
CPCC07K2317/565C07K16/2875C07K2317/56C07K2316/96C07K2317/24C07K2317/76A61P1/00A61P1/04A61P11/00A61P17/02A61P17/06A61P19/02A61P25/00A61P29/00A61P35/00A61P35/02A61P37/00A61P37/02A61P37/06A61P43/00A61P9/10
Inventor 罗杰·史密斯帕拉尼萨姆伊·卡纳卡拉杰维克托·罗施克克雷格·罗森布里奇特·A·库克西
Owner TEVA BIOPHARM USA
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