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Serum albumin binding proteins with long half-lives

A serum albumin and half-life technology, applied in the direction of prolonging plasma life fusion, anti-animal/human immunoglobulin, immunoglobulin, etc., can solve the problems of reducing patient compliance and increasing costs

Inactive Publication Date: 2010-02-10
ABLYNX NV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

All of these factors result in reduced patient compliance and increased costs to the health system

Method used

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  • Serum albumin binding proteins with long half-lives
  • Serum albumin binding proteins with long half-lives
  • Serum albumin binding proteins with long half-lives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0201] Example 1: Identification of Nanobodies Specific for Serum Albumin

[0202] Identification of albumin-specific Nanobodies from camels immunized with human serum albumin. Screening of various Nanobodies is performed by ELISA using human, macaque and mouse albumin, thereby generating a set of Nanobodies that cross-react with serum albumin of different species.

Embodiment 2

[0203] Example 2: Biacore analysis

[0204] The binding of Nanobodies to serum albumin was characterized by surface plasmon resonance in a Biacore 3000 instrument. Serum albumin from different species is covalently bound to the surface of the CM5 sensor chip through amine coupling until an increase of 250 response units is achieved. Inactivate the remaining reaction group. The binding of Nanobodies was evaluated at one concentration (1:20 dilution). Each Nanobody was injected at a flow rate of 45 μl / min for 4 minutes, allowing it to bind to the antigen bound to the chip. At the same flow rate, the Nanobody-free binding buffer was flowed through the chip for 4 hours to allow the bound Nanobody to dissociate spontaneously. Calculate K from sensorgrams obtained for different Nanobodies off -value. Follow K off -Value, for the rating of the tested Nanobody, see Table IV below:

[0205] Table IV:

[0206] Kind

People

Macaque

Mouse

C

PMP6A8

PMP6A8

PMP6B4

C

PMP6B4

...

Embodiment 3

[0212] Example 3: Half-life in rhesus monkeys

[0213] The pharmacokinetic characteristics of trivalent bispecific nanobody constructs including humanized anti-human serum albumin nanobody ALB-8 (SEQ ID NO: 62) were studied in rhesus monkeys. On day 0, three monkeys received the construct at 2 mg / kg. Immediately after application and at 1, 2, 4, 8, 11, and 14 days after application, plasma samples (shown below) were obtained from the rhesus monkeys and analyzed to determine pharmacokinetic characteristics. The PK characteristics in all monkeys are similar, with a calculated half-life of about 10 days. The calculated half-life is within the range of the estimated half-life of macaque albumin.

[0214] Before the environmental adaptation study, the three monkeys were adapted for 4 weeks. On day 0, the monkey was instilled intravenously into the right or left vena cephalica by using an indwelling catheter and an infusion pump, and received the construct at 2 mg / kg. The dose was ad...

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PUM

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Abstract

The present invention relates to amino acid sequences that are capable of binding to serum albumin; to compounds, proteins and polypeptides comprising or essentially consisting of such amino acid sequences; to nucleic acids that encode such amino acid sequences, proteins or polypeptides; to compositions, and in particular pharmaceutical compositions, that comprise such amino acid sequences, proteins and polypeptides; and to uses of such amino acid sequences, proteins and polypeptides.

Description

Invention field [0001] The present invention relates to an amino acid sequence capable of binding to serum albumin; compounds, proteins and polypeptides comprising or consisting essentially of said amino acid sequence; nucleic acids encoding said amino acid sequence, protein or polypeptide; including said amino acid sequence, protein and polypeptide The composition and especially the pharmaceutical composition; and the use of the amino acid sequence, protein and polypeptide. Specifically, the amino acid sequences and compounds of the present invention bind to or otherwise associate with serum albumin in such a way that when the amino acid sequence or compound binds or otherwise associates with serum albumin molecules in primates It shows that the serum half-life is at least 50% of the natural half-life of serum albumin in the primate. [0002] From the further description herein, other aspects, embodiments, advantages and applications of the present invention will become clear. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/18A61K39/395A61P43/00
CPCC07K2319/31C07K2317/31C07K16/18C07K2317/567C07K2317/565C07K2317/92C07K2317/22A61K2039/505C07K2317/24A61P25/00A61P3/10A61P43/00A61P7/00
Inventor 埃尔斯·拜尔内德希尔德·阿迪·皮埃雷特·勒韦兹亨德里克斯·雷内瑞斯·雅各布斯·马托伊斯·霍根博姆海蒂·玛丽亚·弗洛朗斯·约恩克海勒托尔斯滕·德赖尔
Owner ABLYNX NV
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