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Carbonic anhydrase antibody

A carbonic anhydrase and antibody technology, applied in the direction of antibodies, antibody medical components, anti-tumor drugs, etc., can solve problems such as adverse side effects

Active Publication Date: 2015-08-05
慕尼黑赫尔穆侯尔茨中心-德意志健康与环境研究中心(责任有限公司) +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although systemic carbonic anhydrase inhibitors are known in the art, they are associated with adverse side effects such as acid-base imbalance, hypersensitivity and fatal aplasmatic anemia (Gross et al. (1988 ),Am J Opthalmol.,Naeser et al.(1986),Acta Opthalmol.,64:330-337,Mastropasqua et al.(1998),212:318-321;and Passp et al,Br J Opthalmol.1985; 69:572-575)

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0096] Example 1 - CA-XII Expression Levels in Different Types of Human Cancers

[0097] CA-XII is highly expressed in different types of human cancers. Overexpression of CA XII is most pronounced in breast cancer as demonstrated by data documented by Bernett et al. (2008) (available from http: / / ist.genesapiens.org).

Embodiment 2-A549

[0098] Immunofluorescence staining of embodiment 2-A549 cells

[0099] A549 cells were fixed with 4% (v / v) paraformaldehyde (in PBS) for 10 minutes at room temperature, washed with PBS and 0.5% (v / v) Triton-X-100 (in PBS), and Incubate with EXO 6A10 antibody for 60 minutes. After washing with PBS and PBS / 0.5% (v / v) Triton-X-100, cells were incubated with a fluorochrome-labeled secondary antibody (mouse anti-rat IgG / Cy3), and then analyzed by a Leica laser scanning microscope. Bound antibodies were visualized. Nuclei were counterstained with DAPI. Therefore, the staining of CA-XII is clearly associated with the cell membrane of A549 cells ( image 3 ,arrow).

Embodiment 3

[0100] Example 3 - Investigated human cancer cell lines express CA-XII

[0101] refer to Figure 4A , most of the constant human cancer cell lines investigated express CA-XII on the cell surface as shown by flow cytometry. A constant human cancer cell line was incubated on ice with EXO6A10 (hybridoma supernatant diluted 1:5 in 2% (v / v) FCS (e.g., fetal calf serum) in PBS) for 15 minutes, Washed three times in PBS / 2% (v / v) FCS, followed by staining with a specific secondary antibody (goat anti-rat IgG / Cy5) for an additional 15 minutes on ice. Binding of 6A10 was then measured by flow cytometry using a Becton Dickinson FACS Calibur device and FlowJo software (Treestar Corporation). An antibody of the same isotype (glutathione-S-transferase) with an irrelevant specificity was used as a control (gray = isotype control; black line = EXO 6A10). No binding to peripheral blood mononuclear cells (PBMCs) and no binding to two melanoma cell lines (not shown) was detectable. Figure 4...

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Abstract

The present invention relates to an antibody binding to a carbonic anhydrase, wherein the antibody comprises (a) the amino acid sequences SEQ ID NOS. 1 (CDR 1), 2 (CDR 2) and 3 (CDR 3) determining the CDRs of the V H region, and the amino acid sequences SEQ ID NOS. 4 (CDR 1), 5 (CDR 2) and 6 (CDR 3) determining the CDRs of the V L region; or (b) the amino acids sequences of (a), wherein at least one amino acid is conservatively substituted in any one of the amino acid sequences SEQ ID NOS. 1 to 6.

Description

technical field [0001] The present invention relates to an antibody binding to carbonic anhydrase, wherein the antibody comprises: (a) decision V H The amino acid sequences of the CDRs of the regions SEQ ID NO.1 (CDR 1), SEQ ID NO.2 (CDR 2) and SEQ ID NO.3 (CDR 3), and / or determine V L The amino acid sequences of the CDRs of the region are SEQ ID NO.4 (CDR 1), SEQ ID NO.5 (CDR 2) and SEQ ID NO.6 (CDR 3); or, (b) wherein in said amino acid sequence SEQ ID NO . The amino acid sequence of (a) in which at least one amino acid is conservatively substituted in any one of the sequences from 1 to SEQ ID NO.6. Background technique [0002] Throughout this specification, numerous documents are cited, including patent applications and manufacturer's operating manuals. The disclosures of these documents, although we do not believe them to be relevant to the patentability of this invention, are hereby incorporated by reference in their entirety. More specifically, all cited documents ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/395C07K16/30C07K16/40A61P35/00C12N15/00
CPCA61K39/3955A61K39/39558C07K16/40C07K16/30A61P7/06A61P9/00A61P9/02A61P9/10A61P27/02A61P27/06A61P35/00
Inventor 赖因哈德·蔡德勒克里斯蒂娜·巴特克伊莉莎白·克雷默安德鲁·弗拉特利克劳迪乌·苏普兰
Owner 慕尼黑赫尔穆侯尔茨中心-德意志健康与环境研究中心(责任有限公司)