Methods of preventing or treating pain using anti-ngf antibodies

Abstract

Antibodies and antibody fragments thereof with binding specificity to human Nerve Growth Factor (NGF) and methods of use for treating pain. Methods of treating pain or eliciting an analgesic effect comprising administering an effective amount of an anti-human NGF antibody or antibody fragment thereof, which inhibits the association of NGF with TrkA, and/or p75. These methods may optionally further comprising administering an effective amount of a second anti-human NGF antibody or fragment thereof (e.g., one which inhibits the association of NGF with p75, or one that inhibits the association of NGF with TrkA.)

1 . A method of treating pain or eliciting an analgesic effect in an individual, comprising administering an effective amount of at least one anti-human NGF antibody or fragment thereof, wherein the anti-NGF antibody is selected from Ab1, Ab2, Ab5, Ab6, Ab7, Ab8, Ab9, Ab10, Ab11, Ab12, Ab13, Ab14, Ab17, Ab18, Ab19, Ab20, or Ab21, or an antibody or antibody fragment that comprises the same CDRs as anti-NGF antibody is selected from Ab1, Ab2, Ab5, Ab6, Ab7, Ab8, Ab9, Ab10, Ab11, Ab12, Ab13, Ab14, Ab17, Ab18, Ab19, Ab20, or Ab21. 
     
     
         2 . The method of  claim 1 , wherein:
 (i) said antibody or antibody fragment inhibits the association of NGF with TrkA, and the association of NGF with p75;   (ii) the administered antibody or antibody fragment is an anti-NGF antibody or antibody fragment that inhibits the association of NGF with TrkA, and the association of NGF with p75, and further binds to NGF/TrkA complexes and/or NGF/p75 complexes;   (iii) said antibody fragment is a bivalent or monovalent antibody fragment;   (iv) said antibody fragment is a bivalent or monovalent antibody fragment selected from an Fab, Fab′, Fv, scFv fragments, SMIPs (small molecule immunopharmaceuticals), camelbodies, nanobodies, IgNAR, MetMab, or a combination thereof;   (v) the antibody, fragment or monovalent agent is modified to affect circulation time;   (vi) the antibody, fragment or monovalent agent is modified to affect circulation time by the addition of a water soluble polymer such as polyethylene glycol;   (vii) said pain is associated with pre- or post-operative surgery, or pain associated with trauma or injury to the musculoskeletal system prevention or treatment of chronic visceral pain;   (viii) said pain is chronic visceral pain due to a physiological disorder selected from dysmenorrhea, dyspepsia, gastro-esophageal reflux, pancreatitis, visceralgia and irritable bowel syndrome;   (ix) said pain comprises post-surgical pain comprising resting pain or mechanically-induced pain;   (x) the pain comprises thermally-induced pain;   (xi) the subject has a wound and treatment does not inhibit wound healing;   (xii) said pain is selected from pain associated with a cancer, neuropathic pain, and neurogenic pain;   (xiii) said treatment comprises treatment of an acute pain or a chronic pain;   (xiv) the treated pain is a craniofacial pain or a head pain;   (xv) the treated pain is craniofacial pain or the head pain caused by temporomandibular joint disorder (TMJ), migraine or trigeminal neuralgia;   (xvi) the treated pain treated comprises acute pain, dental pain, pain from trauma, surgical pain, pain resulting from amputation or abscess, causalgia, demyelinating diseases, trigeminal neuralgia, cancer, chronic alcoholism, stroke, thalamic pain syndrome, diabetes, acquired immune deficiency syndrome (“AIDS”), toxins, chemotherapy, general headache, migraine, cluster headache, mixed-vascular or non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, lupus, osteoarthritis, fibromyalgia, inflammatory bowel disorders, irritable bowel syndrome, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, sunburn, carditis, dermatitis, myositis, neuritis, collagen vascular diseases, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia or allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, colitis, gastric ulceration, duodenal ulcers, vasomotor or allergic rhinitis, or bronchial disorders, dysmenorrhea, dyspepsia, gastroesophageal reflux, pancreatitis, or visceralgia;   (xvii) administration is effected via craniofacial mucosal administration comprises intranasal administration, buccal administration, sublingual administration or conjunctival administration;   (xviii) the method includes administration of at least one NSAID, optionally selected from the group consisting of ibuprofen, naproxen, naprosyn, diclofenac, ketoprofen, tolmetin, sulindac, mefanamic acid, meclofenamic acid, diflunisal, flufenisal, piroxicam, sudoxicam, isoxicam, celecoxib, fofecoxib, DUP-697, flosulide, meloxicam, 6-methoxy-2-naphthylacetic acid, MK-966, nabumetone, nimesulide, NS-398, SC-5766, SC-58215 and T-614;   (xix) the method is used to treat bone cancer pain, optionally wherein the bone cancer pain is selected from the group consisting of cancer originated in bone or the bone cancer pain is from a cancer metastasized to bone from an undetermined tissue, osteosarcoma, cancer metastasized to bone, prostate cancer metastasized to bone, breast cancer metastasized to bone, lung cancer metastasized to bone, sarcoma metastasized to bone, and renal cancer metastasized to bone;   (xx) the method is used for treating back or neck pain with or without radiculopathy by providing an effective amount of said antibody or fragment to a disc region comprising a a degenerated disc;   (xxi) the antibody is administered via intravenous, subcutaneous, or intranasal administration;   (xxii) the method treats or prevents pain associated with chronic prostatitis and/or chronic pelvic pain syndrome in a subject, optionally wherein said pain associated with chronic prostatitis and/or chronic pelvic pain syndrome is selected from the group comprising lower abdominal (pelvic) pain; lower stomach pain; bladder pain; suprapubic pain; pain in the penis, testicles, scrotum and perineum; urethral pain; dyspareunia; pain, pressure or discomfort that may increase as the bladder fills; dysuria and ejaculatory pain; or   (xxiii) a combination of any of the foregoing.   
     
     
         3 - 29 . (canceled) 
     
     
         30 . The method of  claim 1 , wherein said fragment is a Fab fragment comprising a V H  polypeptide at least 90% identical to one selected from those in SEQ ID NO: 3, 13, 23, 53, 63, 73, 83, 93, 103, 113, 123, 133, 163, 173, 183, 193, or 402 and/or V L  polypeptide sequence at least 90% identical to one selected from: SEQ ID NO: 1, 11, 21, 51, 61, 71, 81, 91, 101, 111, 121, 131, 161, 171, 181, 191, or 401. 
     
     
         31 . The method of  claim 1 , wherein said fragment is a Fab fragment comprising a V H  polypeptide at least 95% identical to one selected from those in SEQ ID NO: 3, 13, 23, 53, 63, 73, 83, 93, 103, 113, 123, 133, 163, 173, 183, 193, or 402 and/or V L  polypeptide sequence at least 95% identical to one selected from: SEQ ID NO: 1, 11, 21, 51, 61, 71, 81, 91, 101, 111, 121, 131, 161, 171, 181, 191, or 401. 
     
     
         32 . The method of  claim 1 , wherein said fragment is a Fab fragment comprising a V H  polypeptide identical to one selected from those in SEQ ID NO: 3, 13, 23, 53, 63, 73, 83, 93, 103, 113, 123, 133, 163, 173, 183, 193, or 402 and/or V L  polypeptide sequence identical to one selected from: SEQ ID NO: 1, 11, 21, 51, 61, 71, 81, 91, 101, 111, 121, 131, 161, 171, 181, 191, or 401. 
     
     
         33 - 36 . (canceled) 
     
     
         37 . The method of  claim 1 , wherein said anti-human NGF antibody or fragment thereof is aglycosylated. 
     
     
         38 . The method of  claim 1 , wherein said antibody contains an Fe region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation. 
     
     
         39 . The method of  claim 1 , wherein said anti-human NGF antibody is human, humanized, single chain, or chimeric. 
     
     
         40 - 42 . (canceled) 
     
     
         43 . The method of  claim 1 , wherein said anti-human NGF antibody or antibody fragment is a Fab comprising the sequences in SEQ ID NO:1 and/or 3; SEQ ID NO:11 and/or 13; SEQ ID NO:21 and/or 23; SEQ ID NO:31 and/or 33: SEQ ID NO:41 and/or 43; SEQ ID NO:51 and/or 53: SEQ ID NO:61 and/or 63: SEQ ID NO:71 and/or 73: SEQ ID NO: 81 and/or 83: SEQ ID NO:91 and/or 93: SEQ ID NO:101 and/or 103: SEQ ID NO:111 and/or 113; SEQ ID NO:121 and/or 123; SEQ ID NO:131 and/or 133: SEQ ID NO:141 and/or 143: SEQ ID NO:151 and/or 153: SEQ ID NO:161 and/or 163: SEQ ID NO:171 and/or 173: SEQ ID NO:181 and/or 183: SEQ ID NO:191 and/or 193: SEQ ID NO:51 and/or 53; SEQ ID NO:405 and/or 406: and SEQ ID NO:407 and/or 408. 
     
     
         44 . The method of  claim 1 , wherein said anti-human NGF antibody or fragment thereof is directly or indirectly attached to a detectable label or therapeutic agent. 
     
     
         45 . The method of  claim 1 , wherein said anti-human NGF antibody or fragment thereof further comprises an effector moiety. 
     
     
         46 . The method of  claim 45 , wherein said effector moiety is a detectable moiety or a functional moiety. 
     
     
         47 . The method of  claim 45 , wherein said detectable moiety is a fluorescent dye, an enzyme, a substrate, a bioluminescent material, a radioactive material, or a chemiluminescent material. 
     
     
         48 . The method of  claim 45 , wherein said functional moiety is streptavidin, avidin, biotin, a cytotoxin, a cytotoxic agent, or a radioactive material. 
     
     
         49 . The method of  claim 1 , further comprising the administration of another therapeutic agent or regimen selected from anti-histamines, anti-inflammatory agents, or antibiotics. 
     
     
         50 . The method of  claim 1 , wherein said anti-human NGF antibody or fragment thereof is contained in a pharmaceutical or diagnostic composition comprising a pharmaceutically acceptable carrier. 
     
     
         51 . The method of  claim 50 , wherein said pharmaceutical or diagnostic composition is lyophilized. 
     
     
         52 . The method of  claim 50 , wherein said pharmaceutical or diagnostic composition comprises one or more anti-human NGF antibodies selected from Ab1, Ab2, Ab5, Ab6, Ab7, Ab8, Ab9, Ab10, Ab11, Ab12, Ab13, Ab14, Ab17, Ab18, Ab19, Ab20, or Ab21, or a humanized, or chimeric variant or fragment thereof. 
     
     
         53 . The method of  claim 1 , wherein the anti-human NGF antibody or fragment thereof consists of an antibody or fragment that inhibits the association of NGF with TrkA and the association of NGF with p75. 
     
     
         54 . The method of  claim 1 , wherein the anti-human NGF antibody or fragment thereof blocks or inhibits the association of NGF with TrkA but does not block or inhibit the association of NGF with p75.