US 12,649,786 B2Granted

Anti-human NR1 antibody derivative

AssigneeArialys Therapeutics, Inc.

InventorsSatoshi Kubo, Atsuo Kanno, Daisuke Yamajuku, Takuya Kito, Masashi Maeda, Takuma Mihara

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Abstract

The present invention addresses the problem of providing a novel therapeutic agent for treating patients with anti NMDAR encephalitis. Patients with an anti NMDAR encephalitis have a pathogenic anti-human NR1 antibody that induces internalization of NMDAR on cell surface. As a result, NMDAR function is weakened in the patients' brain. The present inventors found that the one-armed anti-human NR1 antibody according to the present invention binds to NR1 competitively with the pathogenic anti-human NR1 antibody and inhibits the internalization of NMDAR by the pathogenic anti-human NR1 antibody to thereby exhibit therapeutic effect on anti NMDAR encephalitis. Accordingly, the present invention provides the a one-armed anti-human NR1 antibody, a polynucleotide encoding the antibody, an expression vector containing the polynucleotide, a host cell transformed by the expression vector, a method for producing the antibody, a pharmaceutical composition comprising the antibody, a use of the antibody in the manufacture of the pharmaceutical composition, and a method for treating anti NMDAR encephalitis using the antibody.

Claims20

Dependent claims

An anti-human NR1 antibody comprising an NR1 binding region, the NR1 binding region comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3), selected from:

(1) the HCDR1 consisting of amino acids 31 to 35 of SEQ ID NO:
6, the HCDR2 consisting of amino acids 50 to 66 of SEQ ID NO:
6, the HCDR3 consisting of amino acids 99 to 110 of SEQ ID NO:
6, the LCDR1 consisting of amino acids 24 to 34 of SEQ ID NO:
8, the LCDR2 consisting of amino acids 50 to 56 of SEQ ID NO:
8, and the LCDR3 consisting of amino acid numbers 89 to 98 of SEQ ID NO:
8;
(2) the HCDR1 consisting of amino acids 31 to 36 of SEQ ID NO:
14, the HCDR2 consisting of amino acids 51 to 66 of SEQ ID NO:
14, and the HCDR3 consisting of amino acids of amino acids 99 to 108 of SEQ ID NO:
14, the LCDR1 consisting of amino acids 24 to 34 of SEQ ID NO:
16, the LCDR2 consisting of amino acids 50 to 56 of SEQ ID NO:
16, and the LCDR3 consisting of amino acids 89-97 of SEQ ID NO:
16;
or
(3) the HCDR1 consisting of amino acids 31 to 36 of SEQ ID NO:
18, the HCDR2 consisting of amino acids 51 to 66 of SEQ ID NO:
18, the HCDR3 consisting of amino acids 99 to 108 of SEQ ID NO:
18, the LCDR1 consisting of amino acids 24 to 34 of SEQ ID NO:
20, the LCDR2 consisting of amino acids 50 to 56 of SEQ ID NO:
20, and the LCDR3 consisting of amino acids 89-97 of SEQ ID NO:
20.

19 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/056,635Filed 17 Nov 2022 · continuation
Priority: JP 2020-09210527 May 2020
Published: US 2023/0220070 A113 Jul 2023
Granted: 9 Jun 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification18 codes

C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
A61P 25/00
Drugs for disorders of the nervous system
C07K 16/286
Against receptors, cell surface antigens or cell surface determinants: against neuromediator receptors, e.g. serotonin receptor, dopamine receptor
C12N 15/63
Recombinant DNA-technology: introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression