Granted Patent B2

US 12,747,291 · App. 18/581,446 · Granted Sep 29, 2026

Inventors: Maria-Cristina Loomis (Bothell, WA); Leon F. Garcia-Martinez (Woodinville, WA); Benjamin H. Dutzar (Seattle, WA); Daniel S. Allison (Lake Forest Park, WA); Katherine Lee Hendrix (Renton, WA); Ethan W. Ojala (Snohomish, WA); Pei Fan (Bothell, WA); Jeffrey T.L. Smith (Dublin, IE); John A. Latham (Seattle, WA); Charlie Karasek (Seattle, WA); Jenny Mulligan (Lake Forest Park, WA); Michelle Scalley-Kim (Seattle, WA); Erica Stewart (Seattle, WA); Vanessa Lisbeth Rubin (Seattle, WA); Jens J. Billgren (Seattle, WA)

Assignee: H. LUNDBECK A/S

C07K16/26C07K14/72C12N5/06C12N15/09C12N15/63A61K38/22A61K39/3955A61K2039/505A61P9/08A61P25/06C07K14/575C07K14/70503C07K2317/24C07K2317/34C07K2317/56C07K2317/565C07K2317/76C07K2317/92G01N2333/575Y02A50/30

Abstract

Claims (28)

1 . An isolated nucleic acid or nucleic acids which encode an anti-pituitary adenylate cyclase-activating peptide (anti-PACAP) antibody or antigen binding fragment wherein the encoded antibody or antigen binding fragment comprises

(i) a variable heavy chain comprising a CDR1 consisting of SEQ ID NO: 1284; a CDR2 consisting of SEQ ID NO: 1286; and a CDR3 consisting of SEQ ID NO: 1288; and

(ii) a variable light chain comprising a CDR1 consisting of SEQ ID NO: 1304; a CDR2 consisting of SEQ ID NO: 1306; and a CDR3 consisting of SEQ ID NO: 1308.

2 . An isolated nucleic acid or nucleic acids which encode an anti-pituitary adenylate cyclase-activating peptide (anti-PACAP) antibody or antigen binding fragment according to claim 1 , which comprises a variable heavy chain comprising an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 1282 and a variable light chain comprising an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 1302.

3 . An isolated nucleic acid or nucleic acids which encode an anti-pituitary adenylate cyclase-activating peptide (anti-PACAP) antibody or antigen binding fragment according to claim 1 , which comprises a variable heavy chain comprising an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 1282 and a variable light chain comprising an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 1302.

4 . An isolated nucleic acid or nucleic acids which encode an anti-pituitary adenylate cyclase-activating peptide (anti-PACAP) antibody or antigen binding fragment according to claim 1 , which comprises a variable heavy chain comprising an amino acid sequence with at least 98% sequence identity to SEQ ID NO: 1282 and a variable light chain comprising an amino acid sequence with at least 98% sequence identity to SEQ ID NO: 1302.

5 . An isolated nucleic acid or nucleic acids which encode an anti-pituitary adenylate cyclase-activating peptide (anti-PACAP) antibody or antigen binding fragment according to claim 1 , which comprises a variable heavy chain comprising the amino acid of SEQ ID NO: 1282 and a variable light chain comprising the amino acid of SEQ ID NO: 1302.

6 . An isolated nucleic acid or nucleic acids according to claim 1 , wherein the encoded anti-PACAP antibody or antigen binding fragment:

a.) is chimeric, human or humanized;

b.) is selected from the group consisting of scFvs, nanobodies, Immunoglobulin Previously Presented Antigen Receptors (“IgNARs”), fragment antigen binding (“Fab”) fragments, Fab′ fragments, monovalent antigen binding fragments, and F(ab′) 2 fragments;

c.) substantially or entirely lacks N-glycosylation and/or O-glycosylation;

d.) comprises a human constant domain;

e.) is an IgG1, IgG2, IgG3, or IgG4 antibody;

f.) comprises an Fc region that has been modified to alter at least one of effector function, half-life, proteolysis, or glycosylation,

g.) comprises an Fc region that comprises the sequence of SEQ ID NO: 1244, 1245 or 1246; or

h.) comprises a combination of one or more of a.) to g.).

7 . An expression vector which comprises an isolated nucleic acid or nucleic acids according to claim 1 .

8 . An expression vector which comprises an isolated nucleic acid or nucleic acids according to claim 2 .

9 . An expression vector which comprises an isolated nucleic acid or nucleic acids according to claim 5 .

10 . An isolated recombinant cell which comprises an isolated nucleic acid or nucleic acid according to claim 1 .

11 . An isolated recombinant cell which comprises an isolated nucleic acid or nucleic acids according to claim 2 .

12 . An isolated recombinant cell which comprises an isolated nucleic acid or nucleic acids according to claim 5 .

13 . The isolated recombinant cell according to claim 10 , which comprises a mammalian, bacterial, fungal, yeast, avian, amphibian, plant or insect cell.

14 . The isolated recombinant cell according to claim 10 , which comprises a Chinese Hamster Ovary (CHO) cell.

15 . The isolated recombinant cell according to claim 10 , which comprises a Chinese Hamster Ovary (CHO) cell selected from one of the following subclones or sub-cell lines: DP12 (CHO K1 dhfr-) cell line, NS0 cells, CHO-DXB11 (CHO-DUKX), CHO-pro3, CHO-DG44, CHO 1-15, CHO DP-12, Lec2, M1WT3, Lec8, or pgsA-745.

16 . The isolated recombinant cell according to claim 13 , which comprises a Pichia pastoris, Pichia methanolica or Hansenula polymorpha cell.

17 . A method of expressing an anti-pituitary adenylate cyclase-activating peptide (anti-PACAP) antibody or antigen binding fragment thereof comprising culturing the isolated recombinant cell of claim 10 under conditions that provide for expression of the antibody or antigen binding fragment thereof encoded by said isolated nucleic acid or nucleic acids.

18 . A method of expressing an anti-pituitary adenylate cyclase-activating peptide (anti-PACAP) antibody or antigen binding fragment thereof comprising culturing the isolated recombinant cell of claim 12 under conditions that provide for expression of the antibody or antigen binding fragment thereof encoded by said isolated nucleic acid or nucleic acids.

Continuity (10)

References Cited (168)