Granted Patent B2

US 12,435,129 · App. 17/383,765 · Granted Oct 7, 2025

Inventors: Michael Skov (Belmont, CA); Tarlochan S. Nijjar (Orinda, CA); Sridhar Govindarajan (Los Altos, CA); Tom Purcell (Mountain View, CA); Mark Welch (Fremont, CA); Frédérique Bard (Pacifica, CA); Robin Barbour (Walnut Creek, CA); Wagner Zago (San Carlos, CA)

Assignee: OTHAIR PROTHENA LIMITED

C07K16/18C07K16/2887C07K16/2896C07K16/462A61K2039/505C07K2317/24C07K2317/34C07K2317/55C07K2317/565C07K2317/732C07K2317/734C07K2317/92C07K2319/02C07K2319/30C07K2319/40

Abstract

Claims (20)

1. A nucleic acid encoding a heavy chain variable region and a light chain variable region of an antibody or fragment thereof that specifically binds to Aβ peptide, wherein the heavy chain variable region comprises heavy chain CDR1, CDR2, and CDR3 and the light chain variable region comprises light chain CDR1, CDR2, and CDR3, wherein the heavy chain CDR1, CDR2, and CDR3 and the light chain CDR1, CDR2, and CDR3 are SEQ ID NO: 19 (HCDR1), SEQ ID NO: 21 (HCDR2), and SEQ ID NO: 24 (HCDR3) and SEQ ID NO: 29 (LCDR1), SEQ ID NO: 34 (LCDR2), and SEQ ID NO: 38 (LCDR3).

2. The nucleic acid of claim 1 , wherein the heavy chain variable region, excluding the CDRs, is at least 95% identical an amino acid sequence of SEQ ID NO: 4, and the light chain variable region, excluding the CDRs, is at least 95% identical an amino acid sequence of SEQ ID NO: 9.

3. The nucleic acid of claim 2 , wherein the heavy chain variable region, excluding the CDRs is at least 98% identical to an amino acid sequence selected from SEQ ID NO: 4, and the light chain variable region, excluding the CDRs, is at least 98% identical to an amino acid sequence selected from SEQ ID NO: 9.

4. The nucleic acid of claim 3 , wherein heavy chain variable region is selected from SEQ ID NO: 4, and the light chain variable region is selected from SEQ ID NO: 9.

5. The nucleic acid of claim 1 , wherein the antibody is humanized.

6. The nucleic acid of claim 1 , wherein the antibody is human IgG1.

7. The nucleic acid of claim 1 , wherein the antibody is a full antibody, a chimeric antibody, a CDR-grafted antibody, or a recombinant antibody.

8. The nucleic acid of claim 1 , wherein the fragment is a Fab, Fab′, F(ab′)2, Fabc, or Fv.

9. The nucleic acid of claim 1 further comprising a heavy chain constant region comprising an amino acid sequence at least 95% identical to SEQ ID NO: 40.

10. The nucleic acid of claim 1 further comprising a light chain constant region comprising an amino acid sequence at least 95% identical to SEQ ID NO: 41.

11. The nucleic acid of claim 1 , wherein the antibody specifically binds to an epitope having an amino acid sequence including three or more amino acid positions from amino acids 1-7 of Aβ.

12. A method of producing an antibody or fragment thereof, the method comprising:

(a) culturing cells transformed with the nucleic acid of claim 1 , so that the cells secrete the antibody or fragment thereof encoded by the nucleic acid; and

(b) purifying the antibody or fragment thereof from cell culture.

13. A method of producing a cell line producing an antibody or fragment thereof, the method comprising:

(a) introducing a vector comprising the nucleic acid of claim 1 and a selectable marker into a cell;

(b) propagating the cell under conditions to select for cells having increased copy number of the vector;

(c) isolating single cells from the selected cells; and

(d) banking cells cloned from a single cell selected based on yield of the antibody or fragment thereof encoded by the nucleic acid that is secreted from the cells.

14. The method of claim 13 further comprising propagating the cells under selective conditions and screening for cell lines naturally expressing and secreting at least 100 mg/L/10{circumflex over ( )}6 cells/24 h.

Assignments (22)

Continuity (5)

References Cited (228)