Background: Monoclonal antibodies are a major class of biological therapies in human medicine but have not yet been successfully applied to veterinary species. We have developed a novel approach, PETisation, to rapidly convert antibodies for use in veterinary species. As an example, anti-nerve growth factor (anti-NGF) monoclonal antibodies (mAbs) which are effective in reducing acute and chronic pain in rodents and man are potentially useful for treating pain in dogs but a fully caninised mAb is required in order to avoid an immune response. The aim of this study was to determine the optimal properties of a caninised anti-NGF mAb for safe, repeated administration to dogs, to determine its pharmacokinetic properties and to evaluate its efficacy in a model of inflammatory pain in vivo. Results: Starting with a rat anti-NGF mAb, we used a novel algorithm based on expressed canine immunoglobulin sequences to design and characterise recombinant caninised anti-NGF mAbs. Construction with only 2 of the 4 canine IgG heavy chain isotypes (A and D) resulted in stable antibodies which bound and inhibited NGF with high-affinity and potency but did not bind complement C1q or the high-affinity Fc receptor gamma R1 (CD64). One of the mAbs (NV-01) was selected for scale-up manufacture, purification and pre-clinical evaluation. When administered to dogs, NV-01 was well tolerated, had a long serum half-life of 9 days, was not overtly immunogenic following repeated dosing in the dog and reduced signs of lameness in a kaolin model of inflammatory pain.

BackgroundLimited options are available for the treatment of pain in cats. Monoclonal antibodies (mAbs) that neutralize nerve growth factor (NGF) have demonstrated analgesic capacity in rodent models, people with osteoarthritis, and dogs with degenerative joint disease.Hypothesis/ObjectivesThis 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.AnimalsThirty‐eight cats at a research colony at Charles River Laboratories, Ireland.MethodsFelinized anti‐NGF mAb, NV‐02, was produced using a complementary DNA (cDNA)‐based method (PETization). 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.ResultsAnti‐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 ImportanceThe high affinity, long plasma half‐life, safety, and analgesic efficacy of felinized anti‐NGF mAb (NV‐02) support further investigation of the analgesic potential of this antibody in the cat.