In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti-Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats.
BACKGROUND
Limited 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.


OBJECTIVE
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.


METHODS
Thirty-eight cats at a research colony at Charles River Laboratories, Ireland.


METHODS
Felinized 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.


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
The 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.
Nexvet Australia Pty. Ltd., Melbourne, VIC, Australia.
D P
DP
Gearing
ClinData Services Inc., Fort Collins, CO.
M
M
Huebner
Nexvet Australia Pty. Ltd., Melbourne, VIC, Australia.
E R
ER
Virtue
Nexvet Australia Pty. Ltd., Melbourne, VIC, Australia.
K
K
Knight
Nexvet Australia Pty. Ltd., Melbourne, VIC, Australia.
P
P
Hansen
Comparative Pain Research Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.|Comparative Medicine Institute, North Carolina State University, Raleigh, NC.|Center for Pain Research and Innovation, UNC Chapel Hill, Chapel Hill, NC.
B D X
BD
Lascelles
Ridge Biotechnology, Seattle, WA.
R P
RP
Gearing
Nexvet Australia Pty. Ltd., Melbourne, VIC, Australia.
A C
AC
Drew
D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002371:Cat Diseases / Q000628:therapy*; D002415:Cats; D005260:Female; D007794:Lameness, Animal / Q000628:therapy; D008297:Male; D020932:Nerve Growth Factor / Q000276:immunology*; D010003:Osteoarthritis / Q000628:therapy / Q000662:veterinary*; D059408:Pain Management / Q000662:veterinary; D010148:Intractable Pain / Q000628:therapy / Q000662:veterinary*; D013045:Species Specificity; D016896:Treatment Outcome
D018712:Analgesics, Non-Narcotic; D000911:Antibodies, Monoclonal; D020932:Nerve Growth Factor
Cat pain; Companion animals; Feline analgesia; PETization; Pharmacokinetics