Cancerous disease modifying antibodies

A technology of antibodies and chimeric antibodies, applied in allergic diseases, antibodies, radioactive carriers, etc., can solve problems such as insufficient cancer

Inactive Publication Date: 2009-12-02
F HOFFMANN LA ROCHE & CO AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Second, the assumption that drug molecules that bind to a receptor with the greatest affinity usually have the greatest likelihood of initiating or inhibiting a signal may not always be the case
[0018] With the exception of some advances in the treatment of breast and colon cancers, the identification and development of effective antibody therapies as single agents or co-therapies is insufficient for all types of cancer

Method used

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  • Cancerous disease modifying antibodies
  • Cancerous disease modifying antibodies
  • Cancerous disease modifying antibodies

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0098] Hybridoma production--hybridoma cell line AR27A807.14.1

[0099] According to the Budapest Treaty, the hybridoma cell line AR27A807.14.1 was deposited on July 18, 2006 at the National Microbiology Laboratory, Health Canada, NMLHC, the Canadian International Depository Agency, and the Bureau of Microbiology of the Canadian Ministry of Health. , Health Canada) (1015 Arlington Street, Winnipeg, Manitoba, Canada, R3E 3R2), Accession No. 180706-03. Pursuant to 37 CFR 1.808, the depositor warrants that, at the time of grant of the patent, all constraints imposed on the public availability of the deposited material are irrevocable. If the depositary cannot release a viable sample, replace the deposit.

[0100] To generate hybridomas producing anticancer antibody AR27A807.14.1, single cell suspensions of frozen human colon adenocarcinoma tumor tissue (Genomics Collaborative, Cambridge, MA) were prepared in PBS. Prepare IMMUNEASY by mixing gently TM (Qiagen, Venlo, The Nether...

Embodiment 2

[0107] in vitro binding

[0108] AR27A807.14.1 monoclonal antibody was produced by culturing hybridomas in CL-1000 flasks (BD Biosciences, Oakville, ON), harvested and reseeded twice / week. Standard antibody purification steps were followed using Protein G Sepharose 4 Fast Flow (Amersham Biosciences, Baie d'Urfe, QC). It is within the scope of the invention to use humanized, deimmunized, chimeric or murine monoclonal antibodies.

[0109] Binding of AR27A807.14.1 was assessed by cellular ELISA to: breast cancer (MDA-MB231 and MCF-7), colon cancer (HT-29, Lovo, DLD-1, SW620 and SW1116), prostate cancer (PC-3 ), pancreatic cancer (BxPC-3), and ovarian cancer (OVCAR-3), as well as non-cancer cell lines from the skin (CCD-27sk) and lung (Hs888.Lu). All cell lines were obtained from the American Type Culture Collection (ATCC; Manassas, VA). The same method as described in Example 1 was used except that purified antibody was used at a concentration of 20 μg / mL instead of hybridoma ...

Embodiment 3

[0112] In vivo tumor experiments using DLD-1 cells

[0113] Example 1 demonstrates that AR27A807.14.1 has anticancer properties against some colon cancer cell lines. refer to image 3 and 4 , 4-6 week old female SCID mice were implanted with a 5 million human colon carcinoma cell line (DLD-1 ) in 100 microliters of saline by subcutaneous injection at the nape of the neck. The mice were randomly divided into two treatment groups, 5 in each group. On the day after implantation, in a solution containing 2.7mM KCl, 1mMKH 2 PO 4 , 137mM NaCl and 20mM NaCl 2 HPO 4 After dilution of the diluent from the stock concentrate, each group was administered intraperitoneally with 20 mg / kg AR27A807.14.1 detection antibody or buffer control in a volume of 300 microliters. The antibodies and control samples were then administered in the same manner weekly for the duration of the study. Tumor growth was measured approximately every 7 days with calipers. After 6 antibody injections, the ...

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Abstract

The present invention relates to a method for producing cancerous disease modifying antibodies using a novel paradigm of screening. By segregating the anti-cancer antibodies using cancer cell cytotoxicity as an end point, the process makes possible the production of anti-cancer antibodies for therapeutic and diagnostic purposes. The antibodies can be used in aid of staging and diagnosis of a cancer, and can be used to treat primary tumors and tumor metastases. The anti-cancer antibodies can be conjugated to toxins, enzymes, radioactive compounds, and hematogenous cells.

Description

[0001] Statement of Collaborative Research Agreement [0002] The present invention, as defined by the claims herein, is made within the scope of the parties involved in the joint research agreement (the "Agreement") between Arius Research Inc. and Takeda Pharmaceutical Company Limited produced as a result of activities performed. This Agreement was in effect prior to the date of this invention. field of invention [0003] The present invention relates to the isolation and production of cancerous disease modifying antibodies (CDMABs) and to the use of these CDMABs in therapeutic and diagnostic procedures, optionally in combination with one or more chemotherapeutic agents. The invention also relates to binding assay methods using the CDMABs of the invention. Background of the invention [0004] Monoclonal Antibodies as Cancer Therapy: Every individual with cancer is unique and different from other cancers, as is an individual's identity. Beyond that, current treatments tre...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): C12N5/18A61K39/395A61K47/48A61K51/10A61P35/00A61P37/04C07K16/18C07K16/30C07K16/46C12P21/08G01N33/574G01N33/577
CPCA61K47/48569C07K2317/21C07K16/3046A61K2039/505G01N33/574A61K51/1045C07K16/30A61K47/6851A61P35/00A61P37/04C07K16/18C12N5/16A61K39/395
Inventor戴维·S·F·扬海伦·P·芬德利苏姗·E·哈恩莉萨·M·切凯托
OwnerF HOFFMANN LA ROCHE & CO AG