title: Development of a long acting human growth hormone analog suitable for once a week dosing.
abstract: Human growth hormone was conjugated to a carrier aldolase antibody, using a novel linker by connecting a disulphide bond in growth hormone to a lysine-94 amine located on the Fab arm of the antibody. The resulting CovX body showed reduced affinity towards human growth hormone receptor, reduced cell-based activity, but improved pharmacodynamic properties. We have demonstrated that this CovX-body, given once a week, showed comparable activity as growth hormone given daily in an in vivo hypophysectomized rat model.
authors.affiliation: CovX, Pfizer Worldwide Research and Development, 9381 Judicial Drive, Suite 200, San Diego, CA 92121, USA. Moorthy.palanki@pfizer.com
authors.forename: Moorthy S S
authors.initials: MS
authors.lastname: Palanki
authors.forename: Abhijit
authors.initials: A
authors.lastname: Bhat
authors.forename: Ben
authors.initials: B
authors.lastname: Bolanos
authors.forename: Florence
authors.initials: F
authors.lastname: Brunel
authors.forename: Joselyn
authors.initials: J
authors.lastname: Del Rosario
authors.forename: Danielle
authors.initials: D
authors.lastname: Dettling
authors.forename: Mark
authors.initials: M
authors.lastname: Horn
authors.forename: Rodney
authors.initials: R
authors.lastname: Lappe
authors.forename: Ryan
authors.initials: R
authors.lastname: Preston
authors.forename: Annette
authors.initials: A
authors.lastname: Sievers
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Stankovic
authors.forename: Gary
authors.initials: G
authors.lastname: Woodnut
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D015195:Drug Design; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D006801:Humans; D007016:Hypophysectomy; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D013997:Time Factors
chemical_list: D000906:Antibodies; D019382:Human Growth Hormone; D005634:Fructose-Bisphosphate Aldolase