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Anti-cd160 specific antibodies for the treatment of eye disorders based on neoangiogenesis

A-CD160, eye disease technology, applied in cardiovascular system diseases, antibodies, metabolic diseases, etc., can solve problems such as increasing the risk of harmful events

Inactive Publication Date: 2013-01-23
INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM) +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

To achieve stable results in many patients with wet forms of AMD, up to 24 doses of Avastin may be given over a 2-year period or Lucentis Intravitreal injections are used to treat these patients, which increases the risk of adverse events

Method used

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  • Anti-cd160 specific antibodies for the treatment of eye disorders based on neoangiogenesis
  • Anti-cd160 specific antibodies for the treatment of eye disorders based on neoangiogenesis
  • Anti-cd160 specific antibodies for the treatment of eye disorders based on neoangiogenesis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0120] Materials and methods

[0121] Murine anti-CD160 CL1-R2 mAb. The mouse anti-CD160CL1-R2 mAb (IgG1) was grown in our laboratory and evaluated as an anti-CD160 mAb during the 7th Human Leukocyte Differentiation Antigen Workshop (26). We prepared CL1-R2 mAb from a specific secreting hybridoma cell line by using the high cell density system CeLLine (VALDEA Biosciences). Mouse IgGl isotype control monoclonal antibody He6 was generated by immunizing mice with hepatitis B surface antigen (HB). Both CL1-R2 and IgG1 isotype controls were passed in HiTrap in the purification system TM Affinity chromatography on a protein G column (GE Healthcare) was similarly purified, dialyzed against PBS pH 7.0, concentrated and filtered through a 0.22-μm filter.

[0122] animal. We used BALB / c, C57BL / 6J and NMRI-nu (nu / nu) nude mice (Janvier Laboratories). Mice were 7-10 weeks old, except for those used for ischemic retinopathy experiments, which were 7 days old. Animals were housed in...

Embodiment 2

[0130] Example 2: Synergistic effect of CL1R2 and anti-VEGF antibodies on inhibition of neovascularization

[0131] By using the corneal angiogenesis model with FGF2-treated implants as in Example 1, the inventors evaluated the CL1-R2 mAb in combination with an anti-VEGF antibody (Avastin ) in vivo anti-angiogenic properties.

[0132] For this purpose, they compared the results obtained from several groups of rabbits administered with:

[0133] - IgG1 only (25 μg injected);

[0134] -Avastin only (25 μg injection 2 times);

[0135] - CL1-R2 only (2 injections of 25, 50 or 100 μg);

[0136] -Avastin in combination with IgG1; and

[0137] -Avastin Combined with CL1-R2.

[0138] Each group consisted of 4 rabbits. The grade corresponds to the length of the neovascularization.

[0139] The results are shown in Figure 4 . The inventors demonstrate that using CL1-R2 and anti-VEGF antibodies together provides better results in inhibiting neovascularization in an ocu...

Embodiment 3

[0141] Example 3: Effect of intact and Fab'2 forms of CL1-R2

[0142] The inventors compared the effect of the intact form of CL1-R2 and the Fab'2 form of CL1-R2 on corneal neovascularization. For this purpose they used a control IgG1.

[0143] The results are disclosed in Figure 5. The grade corresponds to the length of the neovascularization. The inventors have shown that the intact form of CL1-R2 provides better results in inhibiting neovascularization than that provided by control IgGl.

[0144] They further demonstrated that the Fab'2 format is very suitable for inhibiting neovascularization as it provided better results compared to the intact form CL1-R2 and control IgG1.

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Abstract

The present invention relates to the use of at least one anti-CD 160 antibody, preferably a compound selected from CL1-R2 monoclonal antibody (which may be obtained by the hybridoma CNCM 1-3204), its conservative fragments and its conservative derivatives, for preparing a drug designed to treat neovascular eye diseases.

Description

technical field [0001] The present invention relates to at least one anti-CD160 antibody, preferably selected from the group consisting of CL1-R2 monoclonal antibody (which can be obtained by hybridoma CNCM I-3204), its conservative fragments and its conservative derivatives in the treatment and / or prevention of neonatal Use in vascular eye diseases. Background technique [0002] The world's leading cause of vision loss - ocular neovascularization occurs in two main parts of the eye: the retina and cornea. [0003] Retinal diseases involving abnormal neovascularization show an increasing incidence in both rich and poor countries. Diabetic retinopathy, exacerbated by abnormal neovascularization, retinopathy of prematurity, and age-related macular degeneration (AMD) in affluent countries constitute an enormous economic burden and two leading causes of low vision and legal blindness worldwide. [0004] Corneal infection or corneal transplantation with abnormal corneal neovasc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P27/02C07K16/28C07K16/22
CPCC07K16/22C07K16/2803A61K2039/507A61K2039/505C07K2317/622C07K2317/73A61P27/02A61P27/06A61P31/00A61P35/00A61P43/00A61P9/00A61P9/10A61P3/10A61K39/395C07K16/28A61K39/3955A61K9/0019A61K9/0048C07K16/2896
Inventor P·勒布泰耶A·邦叙桑
Owner INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
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