Antibodies recognizing tau

A technology of antibody and humanized antibody, which is applied in the direction of antibodies, medical preparations containing active ingredients, anti-animal/human immunoglobulin, etc., and can solve problems such as interference with microtubule assembly and neuronal network destruction

Pending Publication Date: 2021-10-22
PROTHENA BIOSCI LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It has also been reported that hyperphosphorylated tau interferes with microtubule assembly, which may promote disruption of neuronal networks

Method used

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  • Antibodies recognizing tau
  • Antibodies recognizing tau
  • Antibodies recognizing tau

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0516] Example 1. Identification of TAU monoclonal antibody

[0517] A monoclonal antibody for TAU is produced as follows. The 383A.A.Aman Tau (4R0N) [immunogen a] or P301S mutation is lacking the N-terminal His label, lack of N-terminal His label, lack of N-terminal His label, 383A.A. People TAU (4R0N) [Immunogen B] Perform immunization. Immunogen was emulsified in Ribi adjuvants.

Embodiment 2

[0519] Example 2. Top of the antibody 3D6

[0520] A series of overlapping biotinidin peptides across the entire 383AA 4R0n Tau protein were used to make a figure 3D6 antibody. Additional peptides are used to model the potential translational modification of the C-terminus of the protein.

[0521] Biotininic peptide binds to a separate hole of the ELISA tablet of the streptavidin package. The plate was closed and treated with murine 3D6, and then incubated with a mouse antibody conjugated to a horseradish peroxidase. After washed thoroughly, OPD is applied to the tablet and developed. Read the absorbance at 450 nm at 450 nm. The background is reduced by the absorbance value without one-resistant hole, and the threshold of the positive binding is set to 0.2 absorbance units.

[0522] The peptide binding is detected on peptides across (SEQ ID NO: 3) amino acid residues 199-213 and (SEQ ID NO: 3) amino acid residue 262-276. The number of the total length of 4R2N Tau protein (441 amin...

Embodiment 3

[0523] Example 3. Design of humanized 3D6 antibody

[0524] The humanized starting or donor antibody is mouse antibody 3D6. Mature M3D6's heavy chain variable amino acid sequence is provided as SEQ ID NO: 7. Mature M3D6 light chain variable amino acid sequence is provided as SEQ ID NO: 11. The heavy chain Kabat / Chothia complex CDR1, CDR2 and CDR3 amino acid sequences are provided as SEQ ID NO: 8-10, respectively. The light chain Kabatcdr1, CDR2 and CDR3 amino acid sequences are provided as SEQ ID NO: 12-14, respectively. Always use the Kabat number.

[0525] 3D6 variable κ (VK) belongs to the Kabat 2 subgroup of mice, which corresponds to the Kabat 2 subgroup, and the variable heavy chain (VH) belongs to the kabat 2C subgroup of mice, which corresponds to human kabat 1 subgroup [Kabat EA et al, (1991), Sequences of Proteins of Immunological Interest, Fifth Edition NIH Publication 91-3242]. In VK, 16 residue Chothia CDR-L1 belongs to the specification category 4,7 residue Chothia...

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PUM

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Abstract

The invention provides antibodies that specifically bind tau. The antibodies inhibit or delay tau-associated pathologies and associated symptomatic deterioration.

Description

[0001] Cross-reference related application [0002] The present application claims priority to the following patent application: US Temporary Application No. 62 / 813, 126, filed on March 3, 2019, US Temporary Application No. 62 / 813, 137, filed on March 3, 2019, and April 24, 2019 The US Provisional Application No. 62 / 838, 159, which is incorporated by all of these temporary applications for all purposes. [0003] Quote for sequence list [0004] The application includes an electronic sequence list named 536323WO_ST25.TXT, which is created on February 24, 2020 and contains 168,875 bytes, which is incorporated by reference in all purposes. Background technique [0005] TAU is a well-known human protein that can exist in phosphorylation (see, for example, goedert, proc.natl.acad.sci.usa85: 4051-4055 (1988); GoEDERT, EMBO J.8: 393-399 (1989 Lee, Neuron 2: 1615-1624 (1989); GoEDert, Neuron 3: 519-526 (1989); Andreadis, Biochemistry 31: 10626-10633 (1992). It is reported that TAU ​​play a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/18G01N33/68
CPCC07K16/18C07K2317/24C07K2317/92C07K2317/76A61K2039/505A61P25/28C07K2317/30C07K2317/94A61K9/0019A61K45/06C07K2317/565C12N15/63C07K2317/55C07K2317/622
Inventor 塔洛陈·S.·尼扎罗宾·巴伯尔菲利普·詹姆斯·多兰三世刘跃斯维特拉娜·亚历山大马克·E.·伦茨
Owner PROTHENA BIOSCI LTD
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