Unlock instant, AI-driven research and patent intelligence for your innovation.

Antibodies and methods of treating cancer

An antibody, cancer technology, applied in the field of cancer biology

Inactive Publication Date: 2014-09-17
BONOMICS LTD
View PDF157 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, little is known about the function of GPR49

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 and methods of treating cancer
  • Antibodies and methods of treating cancer
  • Antibodies and methods of treating cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0159] Selection of human Fab specific for human GPR49 from a phage display library

[0160] Human antibodies that specifically recognize the extracellular domain of the human GPR49 receptor were isolated using phage display technology.

[0161] Part I: Phage display panning

[0162] Method: Using recombinant human GPR49-Fc ectodomain (GPR49-Fc) (SEQ ID NO: 3) to screen cells containing 3.5x10 10 A native human phagemid Fab library of unique clones (Hoet, R.M., et al. NatBiotechnol. 23(3):344-8 (2005)). Before incubation with the phage library, biotinylated anti-Fc antibodies were captured on magnetic beads, which then captured the GPR49-Fc fusion protein. Selection was performed as described by Hoet et al. After 3 rounds of panning, the 479 bp gene III stump was removed by MluI digestion, and the vector was used for soluble Fab expression in TGI cells.

[0163] Results: 61 unique clones were isolated in this panning. Unique clones were subsequently purified and binding...

Embodiment 2

[0174] Construction of full-length anti-GPR49 IgG

[0175] Methods: Three Fabs were converted into human IgG1 and expressed in CHO cells. DNA sequences encoding 3 different anti-GPR49 Fabs (76C12, 78F05 and 76B04) were isolated from a human antibody phage library (Dyax Corp) by biopanning against the recombinant human GPR49 ectodomain-Fc fusion protein. The Fab gene sequence was used to construct expression plasmids encoding full-length antibodies using the pV90AS expression vector system for antibody production in mammalian cells. pV90AS is a modified pV90 expression vector designed to generate two transcripts from a single promoter by altering the splicing pattern of the primary transcript (see: USPTO application WO2005 / 089285). The native CMV splice donor is spliced ​​into a partially damaged splice acceptor to generate a transcript encoding the antibody light chain, or into a native CMV splice acceptor to generate a transcript encoding the antibody heavy chain. The par...

Embodiment 3

[0180] Construction of full-length anti-GPR49 IgG for increased expression in mammalian cells

[0181] In order to improve the antibody expression yield and product quality, the original VH gene sequences from anti-GPR49Fab76C12, 78F05, 76B04 were modified.

[0182] Methods: First, anti-GPR49 VH sequences were analyzed for sequences containing putative splice sites using public sequence recognition programs (www.tigr.org / tdb / GeneSplicer / gene_spl.html (The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, Md.20850), www.fruitfly.org / seq_tools / splice.html) (Martin G. Reese and Frank H. Eeckman, Lawrence Berkeley National Laboratory, Genome Informatics Group, 1 Cyclotron Road, Berkeley, Calif, 94720; see also, Reese M G, Eeckman, F H, Kulp, D, Haussler, D, 1997. "Improved Splice Site Detection in Genie". J Comp Biol 4(3), 311-23). Second, the heavy chain variable region codons of the anti-GPR49 Fab were replaced with codons corresponding to the same Kabat p...

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

No PUM Login to View More

Abstract

Described herein are antibodies against GPR49 and uses of such antibodies. Various aspects relate to monoclonal, humanized, or fully human antibodies against GPR49, hybridomas or other cell lines expressing such antibodies, nucleic acids and vectors comprising nucleic acids encoding for such antibodies, and methods of treating cancer with such antibodies.

Description

[0001] About the sequence listing [0002] This application is filed electronically together with a Sequence Listing. The sequence listing is provided with the file name BIONO.002WO_Sequence.txt, the file size is about 31 kb, created on October 26, 2012. The information of the sequence listing in electronic form is hereby incorporated by reference in its entirety. [0003] Cross References to Related Applications [0004] This application claims priority to U.S. Provisional Patent Application 61 / 554,436, entitled "METHODS OF TREATING CANCER," filed November 1, 2011, and also claims Priority to U.S. Provisional Patent Application 61 / 554,440 filed entitled "ANTI-GPR49 ANTIBODIES," each of which is hereby incorporated by reference in its entirety. technical field [0005] This application relates generally to the field of cancer biology. More specifically, embodiments relate to anti-GPR49 antibodies and uses of such antibodies. Some embodiments relate to anti-GPR49 monoclona...

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
IPC IPC(8): C07K16/28A61K39/395
CPCC07K2317/55A61K39/39558C07K2317/90C07K16/30C07K2317/76C07K2317/21C07K2317/77A61K2039/505C07K2317/50C07K2317/10C07K16/28C07K2317/567C07K2317/33C07K2317/92A61K31/4745A61P35/00A61K2300/00C07K16/3046
Inventor 克里斯多佛·L·里耶斯彼得·朱谭向阳杨卫星克莉丝蒂琳·格拉夫
Owner BONOMICS LTD