Antibodies that immunospecifically bind to trail receptors

A technology of antibodies and immunoglobulins, applied in the direction of antibodies, immunoglobulins, anti-animal/human immunoglobulins, etc., can solve problems such as increased susceptibility to microbial infections

Inactive Publication Date: 2010-03-24
HUMAN GENOME SCI INC
View PDF126 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Mutations in the p55 receptor lead to increased susceptibility to microbial infection

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Antibodies that immunospecifically bind to trail receptors
  • Antibodies that immunospecifically bind to trail receptors
  • Antibodies that immunospecifically bind to trail receptors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1397] Example 1: Isolation and characterization of the scFv shown in Table 1

[1398] Rescue large scFv libraries

[1399] Use a close to 1×10 11 Antibodies specific to TR4 were selected from a cloned scFv library that was the 1.38 x 10 10 An expanded version of the library (Vaughan et al. (1996), Nature Biotechnology 14:309-314). Rescue the phage by taking 3 × 10 10 Cells were grown in 2YTAG (2YT medium supplemented with 100 μg / ml ampicillin and 2% (w / v) glucose) at 37° C. for 2 hours with shaking. M13K07 helper phage (Stratagene) was added to the cultures at a multiplicity of infection (moi) of approximately 10. The culture was incubated stationary at 37° C. for 15 minutes, followed by gentle aeration (200 rpm) for 45 minutes at the same temperature. The culture was centrifuged and the cells were resuspended in 500 ml 2YTAK (2YT medium supplemented with 100 μg / ml kanamycin) and incubated overnight at 30° C. with good aeration (300 rpm). Phage particles were purified...

Embodiment 2

[1418] Embodiment 2: Biacore analysis of the affinity of TR4 binding polypeptide

[1419] Material

[1420] BIAcore2000 equipment

[1421] BIAcore2000 control software, version 3.1.1

[1422] BIAevaluation, version 3.1

[1423] BIAcore CM5 sensor chip, Cat#BR-1000-14Lot#0364 (BIAcore)

[1424] HBS-EP buffer

[1425] Amine Coupling Kit Cat#BR-1000-50 (BIAcore)

[1426] EDC, #1048-950345 (BIAcore)

[1427] NHS, #1048-950345 (BIAcore)

[1428] Ethanolamine, #1048-950345 (BIAcore)

[1429] 10mM Acetic Acid, pH4.0, Cat#BR1003-50Lot#1821-9503844 (BIAcore)

[1430] TRAIL-FLAG (Alexis Biochemical Cat#522-003-C010#L04793 / a)

[1431] All experiments were performed at 25°C.

[1432] general method

[1433] TR4, TR5, TR7 and TR10 (in the form of Fc fusion protein) were immobilized on the respective flow cells of the BIAcore sensor chip. The TR4-Fcc fusion protein comprises M1-I240 residues of TR4 (SEQ ID NO: 1). Post-translational processing of the entire fusion protein resul...

Embodiment 3

[1448] Example 3: Inhibition of biotinylated TRAIL binding to TR4

[1449] I. Materials:

[1450] 10×PBS (Quality Biological Cat 130-069-161, Lot 708712) Immulon 4 microplate (Dynex Cat 3855, Lot ND540319)

[1451] Bovine serum albumin fraction V (Sigma, #58H0456)

[1452] Trishydroxymethylaminomethane (TRIS BASE)

[1453] Tween20 (Sigma)

[1454] Goat anti-human Fc (Sigma, I-2136, #89H4871)

[1455] TR-4: Fc (as above)

[1456] Biotinylated TRAIL (AM100200-Peprotech)

[1457] HRP-streptavidin (Vector, #L0328)

[1458] TMB Peroxidase Microwell Substrate System (KPL, Kirkegaard & Perry Laboratories Inc.)

[1459] h 2 SO 4 (Fisher)

[1460] 96-well dilution plate (Costar)

[1461] II. Buffer

[1462] Coating buffer (1×PBS)

[1463] Blocking buffer (3% BSA in PBS)

[1464] Universal Diluent (1% BSA in PBST)

[1465] Wash buffer (0.1% Tween20 and 1×PBS)

[1466] III. Method

[1467] Goat anti-human Fc was diluted to 0.1 μg / ml in coating buffer. Immulon 4 microplate...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
molecular weightaaaaaaaaaa
Login to view more

Abstract

The present invention relates to antibodies and related molecules that immunospecifically bind to TRAIL receptor, TR4. Such antibodies have uses, for example, in the prevention and treatment of cancers and other proliferative disorders. The invention also relates to nucleic acid molecules encoding anti-TR4 antibodies, vectors, and host cells containing these nucleic acids, and methods for producing the same. The present invention relates to methods and compositions for preventing, detecting, diagnosing, treating, or ameliorating a disease or disorder, especially cancer and other hyperproliferative disorders, comprising administering to an animal, preferably a human, an effective amount of one or more antibodies or fragments or variants thereof, or related molecules, that immunospecificallybind to TRAIL receptor TR4.

Description

field of invention [0001] The present invention relates to antibodies and related molecules that immunospecifically bind to TRAIL receptor TR4. These antibodies have uses, for example, in the prevention and treatment of cancer and other proliferative diseases. The present invention also relates to nucleic acid molecules encoding anti-TR4 antibodies, vectors and host cells containing these nucleic acids, and methods of producing them. The present invention relates to methods and compositions for preventing, detecting, diagnosing, treating or alleviating diseases or lesions, especially cancer and other hyperproliferative lesions, comprising administering to animals, preferably humans, an effective amount of one or more immunospecifically binding TR4 Antibodies or fragments or variants thereof or related molecules. Background of the invention [0002] Many biological functions such as responses to certain stimuli and natural biological processes are controlled by factors such...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06C07K16/30C07K16/28A61P35/00G01N33/53A61K31/00A61K39/395A61K45/00A61P1/00A61P1/18A61P11/00A61P15/00A61P17/00A61P25/00A61P31/18A61P37/06C12N1/15C12N1/19C12N1/21C12N5/10G01N33/574
CPCA61K39/395C07K16/2878A61K31/00C07K2317/622C07K2317/565A61K2039/505C07K16/30A61K45/06A61P1/00A61P1/18A61P11/00A61P15/00A61P17/00A61P25/00A61P31/18A61P35/00A61P37/06A61P43/00A61K2300/00C07K16/28
Inventor 西奥多拉·萨尔塞多史蒂文·M.·鲁宾克雷格·A.·罗森维维安·R.·艾伯特克莱瑞·路易丝·道森特里斯坦·约翰·沃恩
Owner HUMAN GENOME SCI INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products