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US 10,894,829 B2Granted
Humanized antibody for treating or preventing cognitive disorders, process for producing the same, and agent for treating or preventing cognitive disorders using the same
AssigneesTeijin Pharma Limited, Merck Sharp & Dohme Corp.
InventorsHiroshi Eguchi, Takashi Murakami, Naoko Namiki, Akira Tanokura, Jeanne E. Baker, Sophie Parmentier Batteur, Angela Marie Jablonski, Daniel Stephen Malashock, Carl Mieczkowski, Gopalan (Raghu) Raghunathan
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Abstract
The invention provides methods for using and compositions of humanized antibodies that bind tau protein that is phosphorylated at the serine at position 413.
Claims17
An anti-pSer413 tau antibody or antigen binding fragment thereof comprising:
- (A) a heavy chain variable domain comprising:
- a vhCDR1 comprising an amino acid sequence of SEQ ID NO:86;
- a vhCDR2 comprising an amino acid sequence of SEQ ID NO:115;
- and
- a vhCDR3 comprising an amino acid sequence of SEQ ID NO:88;
- and
- (B) a light chain variable domain comprising a set of vlCDRs selected from the group consisting of:
- (i) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:91;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (ii) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:92;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (iii) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:93;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (vi) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:94;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (v) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:95;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (vi) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:96;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (vii) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:97;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (viii) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:98;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (xi) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:99;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (x) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:100;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (xi) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:101;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- and
- (xii) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:102;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83.
53 more elements
An anti-pSer413 tau antibody or antigen binding fragment thereof comprising:
- (A) a heavy chain variable domain comprising a vhCDR1 comprising an amino acid sequence of SEQ ID NO:86;
- a vhCDR2 comprising an amino acid sequence of SEQ ID NO:115;
- a vhCDR3 comprising an amino acid sequence of SEQ ID NO:88;
- and
- (B) a light chain variable domain comprising a vlCDR1 comprising an amino acid sequence of SEQ ID NO:102;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83.
4 more elements
A humanized antibody, or antigen binding fragment thereof, which causes an antigen-antibody reaction with a tau protein or a tau peptide phosphorylated at least on an amino acid residue corresponding to Ser413 of SEQ ID NO:
- 1, comprising:
- (A) a heavy chain variable domain comprising:
- a vhCDR1 comprising an amino acid sequence of SEQ ID NO:86;
- a vhCDR2 comprising an amino acid sequence of SEQ ID NO:115;
- and
- a vhCDR3 comprising an amino acid sequence of SEQ ID NO:88;
- and
- (B) a light chain variable domain comprising a set of vlCDRs selected from the group consisting of:
- (i) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:91;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (ii) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:92;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (iii) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:93;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (vi) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:94;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (v) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:95;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (vi) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:96;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (vii) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:97;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (viii) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:98;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (xi) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:99;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (x) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:100;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- (xi) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:101;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83;
- and
- (xii) a vlCDR1 comprising an amino acid sequence of SEQ ID NO:102;
- a vlCDR2 comprising an amino acid sequence of SEQ ID NO:82;
- and
- a vlCDR3 comprising an amino acid sequence of SEQ ID NO:83.
54 more elements
A humanized antibody or antigen binding fragment thereof, which causes an antigen-antibody reaction with a tau protein or a tau peptide phosphorylated at least on an amino acid residue corresponding to Ser413 of SEQ ID NO:
- 1, comprising:
- (A) a heavy chain variable domain comprising a vhCDR1 comprising an amino acid sequence of 1M (SEQ ID NO:
- 10);
- a vhCDR2 comprising an amino acid sequence of 2H1 (SEQ ID NO:
- 12) or an amino acid sequence differs from sequence 2H1 (SEQ ID NO:
- 12) in that Ala at position 15 is substituted with Asp;
- a vhCDR3 comprising an amino acid sequence of 3M (SEQ ID NO:
- 13);
- and
- (B) a light chain variable domain comprising a vlCDR1 comprising an amino acid sequence of 4L1 (SEQ ID NO:
- 14) or an amino acid sequence differs from sequence 4L1 (SEQ ID NO:
- 14) in that Ser at position 5 is substituted with Asn;
- a vlCDR2 comprising an amino acid sequence of 5M (SEQ ID NO:
- 16);
- and a vlCDR3 comprising an amino acid sequence of 6M (SEQ ID NO:
- 17).
13 more elements
Dependencies are inferred from the claim text.