Anti-Rho GTPase conformational single domain antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-10544210-B2
Application number	US-201615548578-A
Country	US
Kind code	B2
Filing date	Feb 2, 2016
Priority date	Feb 3, 2015
Publication date	Jan 28, 2020
Grant date	Jan 28, 2020

Abstract

The present invention relates to active form specific anti-Rho GTPase conformational single domain antibodies and their uses in particular in the therapeutic and diagnostic fields. In particular, the present invention relates to a single domain antibody wherein the amino acid sequences of CDR1-IMGT, CDR2-IMGT and CDR3-IMGT have at least 90% of identity with the amino acid sequences of the CDR1-IMGT, CDR2-IMGT and CDR3-IMGT of the H12, B6, 4P75, 4SP1, 4SNP36, 4SNP61, 5SP10, 5SP11, 5SP58, 5SNP47, 5SNP48, 5SNP65, B20, B15, B5, B71, E3, A6, G12, NB61, 212B, 111B or 404F (hs2dAb) single domain antibody which are defined in Table B.

First claim

The invention claimed is:

1. A single domain antibody wherein the amino acid sequences of CDR1-IMGT, CDR2-IMGT and CDR3-IMGT of the single domain antibody are set forth as SEQ ID NOS: 5-7, respectively.

2. The single domain antibody of claim 1 which comprises a framework region FR1 having at least 90% identity with SEQ ID NO:1.

3. The single domain antibody of claim 1 which comprises a framework region FR2 having at least 90% identity with SEQ ID NO:2.

4. The single domain antibody of claim 1 which comprises a framework region FR3 having at least 90% identity with SEQ ID NO:3.

5. The single domain antibody of claim 1 which comprises a framework region FR4 having at least 90% identity with SEQ ID NO:4.

6. The single domain antibody of claim 1 which comprises an amino acid sequence set forth as SEQ ID NO: 62.

7. The single domain antibody of claim 1 which is fused to a heterologous polypeptide to form a fusion protein.

8. The single domain antibody of claim 1 which is fused to an immunoglobulin domain, a single domain antibody, a carrier polypeptide, a fluorescent polypeptide, an enzyme, a polypeptide that facilitates purification or isolation of the fusion protein, a cell-penetrating peptide or an ubiquitin ligase domain.

9. The single domain antibody of claim 1 which is fused to a F-box domain.

10. A method of detecting the presence of at least one activated form of a Rho GTPase, comprising the steps of i) obtaining a sample from a subject, ii) contacting, in vitro, the sample with a single domain antibody of claim 1 , iii) detecting the binding of said single domain antibody to said sample, and iv) comparing the binding detected in step (iii) with a standard, wherein a difference in binding relative to said standard indicates the presence of the at least one activated form of the Rho GTPase in the sample.

Assignees

• Inst Nat Sante Rech Med
• Univ Toulouse 3 Paul Sabatier
• Inst Claudius Regaud
• Univ Toulouse

Inventors

• Olichon Aurelien
• Keller Laura
• Favre Gilles
• Bery Nicolas
• Chinestra Patrick

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K2317/80

  remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title