IP Library Granted Patent US 10,590,191
Granted Patent B2
US 10,590,191 · App. 16/345,279 · Granted Mar 17, 2020

Anti-tau nanobodies

Inventors: Daniel Fagret (La Tronche, FR); Marcelle Moulin (La Tronche, FR); Catherine Ghezzi (La Tronche, FR); Pascale Perret (La Tronche, FR); Sabine Chierici (Grenoble, FR)
Assignees: UNIVERSITE GRENOBLE ALPES; CENTRE HOSPITALIER UNIVERSITAIRE GRENOBLE ALPES; INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)
C07K16/18A61K39/00A61P25/28C12N15/86C07K2317/22C07K2317/569C07K2317/92
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Quick Facts
Patent No.
US 10,590,191
App. No.
16/345,279
Granted
Mar 17, 2020
Kind
B2
Abstract

The invention relates to anti-Tau nanobodies.

Claims (29)

1. A nanobody directed against the Tau protein, said Tau protein being in oligomer form and said nanobody being devoid of a light chain, said nanobody comprising the amino acid sequences:

(i) GRTFSX 1 X 2 X 3 (SEQ ID No. 1) as CDR1 in which the amino acid X 1 is S or R, X 2 is D or Y and X 3 is T or A,

(ii) ISX 1 SGGX 2 T (SEQ ID No. 2) as CDR2 in which the amino acid X 1 is P or R and X 2 is S or V, and

(iii) NRDPKYGNTRY (SEQ ID No. 5) or TARRRISGTPQWHY (SEQ ID No. 8) as CDR3.

2. The nanobody as claimed in claim 1 , said nanobody competing for binding to the Tau protein in oligomer form with a nanobody comprising:

a) the amino acid sequences (i) GRTFSSDT (SEQ ID No. 3) as CDR1, (ii) ISPSGGVT (SEQ ID No. 4) as CDR2 and (iii) NRDPKYGNTRY (SEQ ID No. 5) as CDR3; or

b) the amino acid sequences (i) GRTFSRYA (SEQ ID No. 6) as CDR1, (ii) ISRSGGST (SEQ ID No. 7) as CDR2 and (iii) TARRRISGTPQWHY (SEQ ID No. 8) as CDR3.

3. The nanobody as claimed in claim 1 , said nanobody comprising:

a) the amino acid sequences (i) GRTFSSDT (SEQ ID No. 3) as CDR1, (ii) ISPSGGVT (SEQ ID No. 4) as CDR2 and (iii) NRDPKYGNTRY (SEQ ID No. 5) as CDR3; or

b) the amino acid sequences (i) GRTFSRYA (SEQ ID No. 6) as CDR1, (ii) ISRSGGST (SEQ ID No. 7) as CDR2 and (iii) TARRRISGTPQWHY (SEQ ID No. 8) as CDR3.

4. The nanobody as claimed in claim 1 , said nanobody comprising the amino acid sequences SEQ ID No. 9 or SEQ ID No. 10.

5. The nanobody as claimed in claim 4 , said nanobody comprising an amino acid sequence consisting of SEQ ID No. 9.

6. The nanobody as claimed in claim 1 , said nanobody being bound to a detectable marker.

7. The nanobody as claimed in claim 6 , said detectable marker being a radioelement.

8. A pharmaceutical composition comprising the nanobody as claimed in claim 1 in combination with a pharmaceutically acceptable carrier.

9. A nucleic acid comprising a nucleic acid sequence encoding the nanobody as claimed in claim 1 .

10. A vector comprising the nucleic acid as claimed in claim 9 .

11. A cell comprising the nucleic acid as claimed in claim 9 .

12. A method for producing a nanobody, said method comprising:

(i) culturing the cell as claimed in claim 11 , under conditions suitable for allowing the expression of said nanobody, and

(ii) recovering the nanobody expressed.

13. A method of inhibiting progression of Tau aggregation comprising administering to a subject the nanobody as claimed in claim 1 .

14. A method for noninvasive, in vivo medical imaging, comprising administering to a subject the nanobody as claimed in claim 1 ; and detecting binding or absence of binding of the nanobody in an area of the subject's body.

15. A method for diagnosis of a tauopathy comprising administering to a subject the nanobody as claimed in claim 1 ; detecting said nanobody in the subject's body; and diagnosing the subject as having a tauopathy or at risk of a tauopathy when the amount of said nanobody detected in the brain is greater than the background noise which corresponds to a nonspecific location of the nanobody in the body.

16. A method of in vitro detection of the Tau protein in oligomer form in a sample comprising contacting an in vitro sample with the nanobody as claimed in claim 1 ; and detecting the nanobody bound to Tau protein in oligomer form in the sample.

17. A method for producing a recombinant host cell expressing a nanobody, said method comprising:

(i) introducing, in vitro or ex vivo, a nucleic acid comprising a nucleic sequence encoding the nanobody as claimed in claim 1 into a competent host cell,

(ii) culturing, in vitro or ex vivo, the recombinant host cell obtained, and

(iii) optionally selecting the cells which express and/or secrete said nanobody.

Assignments (2)
MERGER Recorded Jun 29, 2022
From: UNIVERSITÉ GRENOBLE ALPES (SIREN NO. 130 021 397)
To: UNIVERSITÉ GRENOBLE ALPES (SIREN NO. 130 026 081)
Reel/Frame 060528/0718 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 21, 2019
From: FAGRET, DANIEL; MOULIN, MARCELLE; GHEZZI, CATHERINE; PERRET, PASCALE; CHIERICI, SABINE
To: UNIVERSITE GRENOBLE ALPES; CENTRE HOSPITALIER UNIVERSITAIRE GRENOBLE ALPES; INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)
Reel/Frame 050778/0684 →
Priority Claims (1)
FR 16 60450 · Oct 27, 2016 · national
Continuity (1)
Related Publication 20190263898A1 · Aug 29, 2019
Cited By (1)
US 12,466,854