Chimeric therapeutic anti-CD37 antibodie HH1

A chimeric antibody, CD37 technology, applied in the direction of antibody, radioactive carrier, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, etc.

Inactive Publication Date: 2014-10-22
NORDIC NANOVECTOR
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0018] Others have also disclosed anti-CD37 mAbs that showed potential (eg WO2009 / 019312 to Heider et al. and WO 2011 / 092295 to the present inventors), but after demonstrating that CD37 is CD20 for the treatment of B-cell malignancies There is still a long way to go before an ideal replacement for

Method used

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  • Chimeric therapeutic anti-CD37 antibodie HH1
  • Chimeric therapeutic anti-CD37 antibodie HH1
  • Chimeric therapeutic anti-CD37 antibodie HH1

Examples

Experimental program
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Effect test

Embodiment 1

[0250] The preparation of embodiment 1 chimeric antibody

[0251] Using an expression vector for the V-region gene, a chimeric form of the HH1 antibody was prepared.

[0252] This vector accepts VH and VL chain genes obtained by RT-PCR.

[0253] Then the V-genes were sequenced, and new specific primers were designed to amplify the V-genes, and then they were cloned into the pLNOH2 vector containing human IgG antibody constant region genes (Cγ3, Cγ1 and CH1γ3).

[0254] The pLNOH2 vector comprising the constant regions IgG1CH1 (SEQ ID NO.5), IgG1CH2 (SEQ ID NO.6), IgG1CH3 (SEQ ID NO.7) is shown in SEQ ID NO.8.

[0255] The heavy and light chains of the vector pLNOH2 (SEQ ID NO. 5) and pLNOκ were combined to prepare the combined vector pLNOH2γ1 / καCD37. The entire light chain gene (SEQ ID NO: 9), the CMV promoter and the polyA signal of pLNOκαCD37 were subcloned into pLNOH2hIgG1αCD37.

[0256] In combinatorial vectors, the heavy and light chains are expressed from their own CM...

Embodiment 2

[0270] Example 2 Flow Cytometry for Assessing Antigen Binding

[0271] Binding analysis of hchIgG1ααCD37b(chHH1) to Daudi cells expressing CD37

[0272] Cells were stained and fixed.

[0273] The target binding of the constructed chHH1 was analyzed by flow cytometry. Daudi cells expressing CD37 were stained with chHH1 or hIgG1αNIP. In the left panel, intact Daudi cells were selected, and in the right panel the fluorescence histograms of these stained cells are shown. chHH1 bound to Daudi cells expressing CD37 (solid line), while chimeric αNIP IgG 1 No binding (dashed line).

Embodiment 3

[0274] Example 3 Radiolabeling of Chimeric HH1

[0275] Iodination: According to the manufacturer's instructions, using IODOGEN pre-coated iodination test tubes (Pierce, Rockford, IL), by indirect iodination method with 125 I label the antibody.

[0276] use 111 In and 177 Labeling with Lu: First react the antibody with a chelator (p-SCN-Bn-DTPA or p-SCN-Bn-DOTA).

[0277] The DTPA or DOTA chelator was dissolved in 0.05M HCl, then added to the antibody, and the pH was adjusted to approximately 8.5 by washing with carbonate buffer at a ratio of 5:1. The pH is then checked again and adjusted if necessary. The solution was shaken at room temperature for 60 minutes, and then the reaction was stopped by adding 50 μl of 200 mM glycine solution (per mg antibody).

[0278] To remove free chelator, the conjugated antibody was washed 4-5 times with PBS (PAA), then adjusted to pH 5 by washing with ammonium acetate. followed by 111 In or 177 Lu (Perkin Elmer, Boston, Ma, USA) was ...

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Abstract

The present invention relates to chimieric or humanized antibodies derived from the mouse monoclonal antibody HH1. The applications of the present invention include therapeutic applications in which pharmaceutical compositions comprising the antibodies of the present invention or radioimmunoconjugates hereof are used for treating B-cell malignancies.

Description

technical field [0001] The present invention relates to immunotherapy and radioimmunotherapy of chimeric or humanized antibodies with unexpectedly high cytotoxicity against hematological cancers and different applications of said antibodies. Background technique [0002] The present invention relates to chimeric and humanized anti-CD37 antibodies and their production and use. [0003] Furthermore, the present invention relates to immunotherapy and radioimmunotherapy based on B-cell depletion. [0004] In particular, the invention relates to anti-CD37 antibody molecules for use in such therapies, eg, for the treatment of B cell malignancies and autoimmune conditions. [0005] Immunotherapy using monoclonal antibodies (mAbs) has emerged as a safe and selective approach for the treatment of cancer and other diseases. [0006] Specifically, the use of monoclonal antibodies in B-cell depletion-based therapies (e.g., in B-cell in the treatment of cellular malignancies). [000...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/10C07K16/28
CPCC07K16/2896C07K2317/734A61K51/1027A61K2039/507C07K2317/732C07K2317/94A61K2039/505C07K16/2887C07K2317/24A61P35/00A61P35/02A61P43/00
Inventor 罗伊·H·拉森约斯泰因·达勒
Owner NORDIC NANOVECTOR
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