METHODS OF PREVENTING INFLAMMATION AND TREATING PAIN USING ANTI-NGF COMPOSITIONS
This invention pertains to monovalent agents, including Fab fragments and monovalent monoclonal antibodies analogous to MetMab, having binding specificity to human Nerve Growth Factor (“NGF”), and methods of treating pain in an individual wherein there is no substantial increase in the inflammatory response of the individual following administration of the monovalent agents.
1 . A method of treating pain in an individual, comprising administering a therapeutically effective amount of an anti-human NGF monovalent agent having binding specificity for NGF that does not substantially increase the inflammatory response of a patient following administration of said monovalent agent.
2 . The method of claim 1 , wherein said monovalent agent is an Fab, Fab′, Fv, scFv fragment, SMIP (small molecule immunopharmaceutical), camelbody, nanobody, IgNAR, a monovalent antibody molecule analagous to MetMab, or one or more combinations thereof.
3 . The method of claim 1 , wherein the monovalent agent is a Fab antibody fragment comprising a variable light chain comprising the CDR 1 sequence of SEQ ID NO:55, the CDR 2 sequence of SEQ ID NO:56, and the CDR 3 sequence of SEQ ID NO:57, and/or a variable heavy chain comprising the CDR 1 sequence of SEQ ID NO:58, the CDR 2 sequence of SEQ ID NO:59, and the CDR 3 sequence of SEQ ID NO:60.
4 . The method of claim 1 , wherein the monovalent agent is a Fab antibody fragment or Fab′, Fv, scFv fragment, SMIP (small molecule immunopharmaceutical), camelbody, nanobody, IgNAR, or a monovalent antibody comprising the same the CDRS contained in any one of antibodies Ab1, Ab2, Ab3, Ab4, Ab5, Ab6, Ab7, Ab8, Ab9, Ab10, Ab11, Ab12, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab20 or Ab21.
5 . The method of claim 4 , wherein the Fab antibody fragment is obtained by papain digestion of any one of antibodies Ab1, Ab2, Ab3, Ab4, Ab5, Ab6, Ab7, Ab8, Ab9, Ab10, Ab11, Ab12, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab20 or Ab21.
6 . The method of claim 1 , wherein the anti-human NGF monovalent agent is a monovalent anti-NGF antibody which comprises the same CDR polypeptides as an anti-human NGF antibody selected from Ab1, Ab2, Ab3, Ab4, Ab5, Ab6, Ab7, Ab8, Ab9, Ab10, Ab11, Ab12, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab20 or Ab21.
7 - 9 . (canceled)
10 . The method of claim 1 , wherein said anti-human NGF monovalent agent 1s aglycosylated.
11 - 13 . (canceled)
14 . The method of claim 1 , wherein said anti-human NGF monovalent agent further comprises an effector moiety.
15 . The method of claim 14 , wherein said effector moiety is a detectable moiety or a functional moiety.
16 - 17 . (canceled)
18 . The method of claim 1 , further comprising the administration of another therapeutic agent or regimen selected from analgesic agents, anti-histamines, anti-inflammatory agents, or antibiotics.
19 - 21 . (canceled)
22 . The method of claim 1 , wherein the pain is selected from inflammatory pain, post-operative incision pain, complex regional pain syndrome, cancer pain, primary or metastatic bone cancer pain, fracture pain, osteoporotic fracture pain, pain resulting from burn, osteoporosis, gout joint pain, pain associated with sickle cell crises, and other nociceptic pain, as well as hepatocellular carcinoma, breast cancer, liver cirrhosis, neurogenic pain, neuropathic pain, nociceptic pain, trigeminal neuralgia, post-herpetic neuralgia, phantom limb pain, fibromyalgia, menstrual pain, ovarialgia, reflex sympathetic dystrophy, neurogenic pain, osteoarthritis or rheumatoid arthritis pain, lower back pain, diabetic neuropathy, sciatica, or migraine.
23 . The method of claim 1 , wherein said pain is associated with pre- or post-operative surgery or post-operative pain, or pain associated with trauma or injury to the musculoskeletal system prevention or treatment of chronic visceral pain.
24 - 28 . (canceled)
29 . The method of claim 1 , wherein said pain includes pain associated with a cancer, neuropathic pain, and/or neurogenic pain.
30 . The method of claim 1 , wherein said treatment comprises treatment of an acute pain or a chronic pain.
31 . The method of claim 1 , wherein the pain is a craniofacial pain or a head pain.
32 . The method of claim 31 , wherein the craniofacial pain or the head pain is caused by temporomandibular joint disorder (TMJ), migraine or trigeminal neuralgia.
33 - 37 . (canceled)
38 . The method of claim 1 , wherein said anti-human NGF monovalent agent having binding specificity for NGF, blocks or inhibits the interaction of NGF with TrkA and/or p75.
39 . (canceled)
40 . The method of claim 38 , wherein said anti-human NGF monovalent agent having binding specificity for NGF, blocks or inhibits the interaction of NGF with TrkA but does not block or inhibit the interaction of NGF with p75.