Open AccessIn Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti‐Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats
Author(s) -
Gearing D.P.,
Huebner M.,
Virtue E.R.,
Knight K.,
Hansen P.,
Lascelles B.D.X.,
Gearing R.P.,
Drew A.C.
Publication year - 2016
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/jvim.13985
Subject(s) - medicine , in vivo , nerve growth factor , potency , pharmacokinetics , analgesic , monoclonal antibody , pharmacology , antibody , in vitro , osteoarthritis , nociception , cats , inflammation , immunology , pathology , receptor , biology , biochemistry , microbiology and biotechnology , alternative medicine
Background Limited options are available for the treatment of pain in cats. Monoclonal antibodies ( mA bs) that neutralize nerve growth factor ( NGF ) have demonstrated analgesic capacity in rodent models, people with osteoarthritis, and dogs with degenerative joint disease. Hypothesis/Objectives This study describes the design and characterization of a fully felinized anti‐ NGF monoclonal antibody. In vitro potency, pharmacokinetics, and the ability of the antibody to treat pain in a self‐resolving, acute inflammation model were investigated in cats. Animals Thirty‐eight cats at a research colony at Charles River Laboratories, Ireland. Methods Felinized anti‐ NGF mA b, NV ‐02, was produced using a complementary DNA ( cDNA )‐based method ( PET ization). Purified NV ‐02 was tested for affinity, potency, and immunoreactivity in vitro, then for safety and plasma pharmacokinetic distribution in vivo, and analgesic efficacy in a model of kaolin‐induced inflammatory pain. Results Anti‐NGF mAb, NV ‐02 neutralized NGF with high affinity and potency and did not bind complement. NV ‐02‐administered SC had a plasma half‐life of 7–15 days and was well tolerated at dosages up to 28 mg/kg. A dosage of 2 mg/kg NV ‐02 SC significantly decreased signs of lameness on day 2 ( P = .0027), day 3 ( P = .016), day 4, ( P = .0063), day 5 ( P = .0085), day 6 ( P = .0014), and day 7 ( P = .0034) after induction of inflammation. Conclusions and Clinical Importance The high affinity, long plasma half‐life, safety, and analgesic efficacy of felinized anti‐ NGF mA b ( NV ‐02) support further investigation of the analgesic potential of this antibody in the cat.