JP5719596B2 - 抗体及びその誘導体 - Google Patents
抗体及びその誘導体 Download PDFInfo
- Publication number
- JP5719596B2 JP5719596B2 JP2010544733A JP2010544733A JP5719596B2 JP 5719596 B2 JP5719596 B2 JP 5719596B2 JP 2010544733 A JP2010544733 A JP 2010544733A JP 2010544733 A JP2010544733 A JP 2010544733A JP 5719596 B2 JP5719596 B2 JP 5719596B2
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- derivative
- antibodies
- pain
- trka
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 208000002193 Pain Diseases 0.000 claims description 48
- 230000027455 binding Effects 0.000 claims description 48
- 238000011282 treatment Methods 0.000 claims description 40
- 230000036407 pain Effects 0.000 claims description 36
- 239000012634 fragment Substances 0.000 claims description 30
- 230000014509 gene expression Effects 0.000 claims description 22
- 150000007523 nucleic acids Chemical class 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 108020004707 nucleic acids Proteins 0.000 claims description 18
- 102000039446 nucleic acids Human genes 0.000 claims description 18
- 238000001943 fluorescence-activated cell sorting Methods 0.000 claims description 17
- 208000035475 disorder Diseases 0.000 claims description 15
- 206010028980 Neoplasm Diseases 0.000 claims description 14
- 238000003556 assay Methods 0.000 claims description 14
- 230000000694 effects Effects 0.000 claims description 14
- 230000004927 fusion Effects 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- 230000000202 analgesic effect Effects 0.000 claims description 10
- 208000000094 Chronic Pain Diseases 0.000 claims description 8
- 230000004071 biological effect Effects 0.000 claims description 7
- 229920001184 polypeptide Polymers 0.000 claims description 7
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 7
- 230000009261 transgenic effect Effects 0.000 claims description 7
- 102000015533 trkA Receptor Human genes 0.000 claims description 7
- 108010064884 trkA Receptor Proteins 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 208000027418 Wounds and injury Diseases 0.000 claims description 5
- 238000003745 diagnosis Methods 0.000 claims description 5
- 208000014674 injury Diseases 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- 208000004296 neuralgia Diseases 0.000 claims description 5
- 208000021722 neuropathic pain Diseases 0.000 claims description 5
- 239000013598 vector Substances 0.000 claims description 5
- 206010024229 Leprosy Diseases 0.000 claims description 4
- 101150056950 Ntrk2 gene Proteins 0.000 claims description 4
- 208000005298 acute pain Diseases 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 230000006378 damage Effects 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 230000005847 immunogenicity Effects 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 230000007170 pathology Effects 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 238000004393 prognosis Methods 0.000 claims description 4
- 238000000159 protein binding assay Methods 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 206010027476 Metastases Diseases 0.000 claims description 3
- 241000283984 Rodentia Species 0.000 claims description 3
- 238000002372 labelling Methods 0.000 claims description 3
- 230000009401 metastasis Effects 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 238000010186 staining Methods 0.000 claims description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 101710112752 Cytotoxin Proteins 0.000 claims description 2
- 208000005171 Dysmenorrhea Diseases 0.000 claims description 2
- 206010013935 Dysmenorrhoea Diseases 0.000 claims description 2
- 201000009273 Endometriosis Diseases 0.000 claims description 2
- 208000031886 HIV Infections Diseases 0.000 claims description 2
- 208000037357 HIV infectious disease Diseases 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 208000005615 Interstitial Cystitis Diseases 0.000 claims description 2
- 206010024453 Ligament sprain Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 206010028391 Musculoskeletal Pain Diseases 0.000 claims description 2
- 208000023178 Musculoskeletal disease Diseases 0.000 claims description 2
- 206010033645 Pancreatitis Diseases 0.000 claims description 2
- 208000004550 Postoperative Pain Diseases 0.000 claims description 2
- 206010060932 Postoperative adhesion Diseases 0.000 claims description 2
- 208000010040 Sprains and Strains Diseases 0.000 claims description 2
- 206010045171 Tumour pain Diseases 0.000 claims description 2
- 206010053692 Wound complication Diseases 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 239000000730 antalgic agent Substances 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims description 2
- 201000003146 cystitis Diseases 0.000 claims description 2
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 2
- 239000002619 cytotoxin Substances 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 208000017445 musculoskeletal system disease Diseases 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 208000025661 ovarian cyst Diseases 0.000 claims description 2
- 201000007094 prostatitis Diseases 0.000 claims description 2
- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 2
- 208000009935 visceral pain Diseases 0.000 claims description 2
- 239000004020 conductor Substances 0.000 claims 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 241000124008 Mammalia Species 0.000 claims 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims 2
- 101150111783 NTRK1 gene Proteins 0.000 claims 1
- 229940035676 analgesics Drugs 0.000 claims 1
- 201000001883 cholelithiasis Diseases 0.000 claims 1
- 230000006698 induction Effects 0.000 claims 1
- 201000001119 neuropathy Diseases 0.000 claims 1
- 230000007823 neuropathy Effects 0.000 claims 1
- 208000033808 peripheral neuropathy Diseases 0.000 claims 1
- 230000003612 virological effect Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 63
- 102100023995 Beta-nerve growth factor Human genes 0.000 description 40
- 108010025020 Nerve Growth Factor Proteins 0.000 description 39
- 229940053128 nerve growth factor Drugs 0.000 description 39
- 150000001413 amino acids Chemical class 0.000 description 34
- 235000001014 amino acid Nutrition 0.000 description 27
- 238000002347 injection Methods 0.000 description 24
- 239000007924 injection Substances 0.000 description 24
- 241000699666 Mus <mouse, genus> Species 0.000 description 22
- 238000000034 method Methods 0.000 description 21
- 229940024606 amino acid Drugs 0.000 description 19
- 239000000872 buffer Substances 0.000 description 18
- 210000002683 foot Anatomy 0.000 description 18
- 208000004454 Hyperalgesia Diseases 0.000 description 16
- 102100024952 Protein CBFA2T1 Human genes 0.000 description 16
- 238000002474 experimental method Methods 0.000 description 16
- 230000004044 response Effects 0.000 description 15
- 239000006228 supernatant Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 208000035154 Hyperesthesia Diseases 0.000 description 14
- 239000000427 antigen Substances 0.000 description 13
- 239000000523 sample Substances 0.000 description 13
- 238000006467 substitution reaction Methods 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 12
- 108091007433 antigens Proteins 0.000 description 12
- 102000036639 antigens Human genes 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 230000035772 mutation Effects 0.000 description 11
- 230000004913 activation Effects 0.000 description 10
- 239000000556 agonist Substances 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- 108060003951 Immunoglobulin Proteins 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- 102000018358 immunoglobulin Human genes 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 239000013642 negative control Substances 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- 108020001507 fusion proteins Proteins 0.000 description 8
- 102000037865 fusion proteins Human genes 0.000 description 8
- 210000003630 histaminocyte Anatomy 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000007910 systemic administration Methods 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 7
- 108010029485 Protein Isoforms Proteins 0.000 description 7
- 102000001708 Protein Isoforms Human genes 0.000 description 7
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 7
- 230000003447 ipsilateral effect Effects 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 206010070834 Sensitisation Diseases 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- 238000002648 combination therapy Methods 0.000 description 6
- 230000000295 complement effect Effects 0.000 description 6
- 238000007912 intraperitoneal administration Methods 0.000 description 6
- 230000008533 pain sensitivity Effects 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 230000008313 sensitization Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 101100221606 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS7 gene Proteins 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 230000003040 nociceptive effect Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 239000003053 toxin Substances 0.000 description 5
- 231100000765 toxin Toxicity 0.000 description 5
- 108700012359 toxins Proteins 0.000 description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 102000009109 Fc receptors Human genes 0.000 description 4
- 108010087819 Fc receptors Proteins 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 208000028389 Nerve injury Diseases 0.000 description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000003070 anti-hyperalgesia Effects 0.000 description 4
- 230000003542 behavioural effect Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 210000000548 hind-foot Anatomy 0.000 description 4
- 210000004408 hybridoma Anatomy 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 230000008764 nerve damage Effects 0.000 description 4
- 201000002528 pancreatic cancer Diseases 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 238000003260 vortexing Methods 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 101001111439 Homo sapiens Beta-nerve growth factor Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 206010065390 Inflammatory pain Diseases 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 244000208734 Pisonia aculeata Species 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 108700019146 Transgenes Proteins 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000011260 co-administration Methods 0.000 description 3
- 230000024203 complement activation Effects 0.000 description 3
- 230000004154 complement system Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 230000002637 immunotoxin Effects 0.000 description 3
- 239000002596 immunotoxin Substances 0.000 description 3
- 231100000608 immunotoxin Toxicity 0.000 description 3
- 229940051026 immunotoxin Drugs 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 238000007427 paired t-test Methods 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 239000011534 wash buffer Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 241000283707 Capra Species 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 241000283074 Equus asinus Species 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 101001074035 Homo sapiens Zinc finger protein GLI2 Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 241000282560 Macaca mulatta Species 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 208000005890 Neuroma Diseases 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 2
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 102100035558 Zinc finger protein GLI2 Human genes 0.000 description 2
- 206010053552 allodynia Diseases 0.000 description 2
- 206010002512 anhidrosis Diseases 0.000 description 2
- 230000037001 anhydrosis Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 230000007012 clinical effect Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 210000004602 germ cell Anatomy 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 238000011694 lewis rat Methods 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 108020004084 membrane receptors Proteins 0.000 description 2
- 102000006240 membrane receptors Human genes 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 210000004126 nerve fiber Anatomy 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000000014 opioid analgesic Substances 0.000 description 2
- 229940005483 opioid analgesics Drugs 0.000 description 2
- 230000008058 pain sensation Effects 0.000 description 2
- 230000005298 paramagnetic effect Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 208000023958 prostate neoplasm Diseases 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000003118 sandwich ELISA Methods 0.000 description 2
- 210000003497 sciatic nerve Anatomy 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- 230000010474 transient expression Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
- WUAPFZMCVAUBPE-NJFSPNSNSA-N 188Re Chemical compound [188Re] WUAPFZMCVAUBPE-NJFSPNSNSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 206010000871 Acute monocytic leukaemia Diseases 0.000 description 1
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 208000036487 Arthropathies Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 101710129634 Beta-nerve growth factor Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 108700012434 CCL3 Proteins 0.000 description 1
- 101100180402 Caenorhabditis elegans jun-1 gene Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010064012 Central pain syndrome Diseases 0.000 description 1
- 102000000013 Chemokine CCL3 Human genes 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102000014447 Complement C1q Human genes 0.000 description 1
- 108010078043 Complement C1q Proteins 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 208000006509 Congenital Pain Insensitivity Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 238000003591 CyQUANT Cell Proliferation Assay Kit Methods 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 206010061619 Deformity Diseases 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
- 208000036566 Erythroleukaemia Diseases 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000777471 Homo sapiens C-C motif chemokine 4 Proteins 0.000 description 1
- 101100310327 Homo sapiens MAPKAP1 gene Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 208000008017 Hypohidrosis Diseases 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 description 1
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 1
- IDBPHNDTYPBSNI-UHFFFAOYSA-N N-(1-(2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl)-4-(methoxymethyl)-4-piperidyl)propionanilide Chemical compound C1CN(CCN2C(N(CC)N=N2)=O)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 IDBPHNDTYPBSNI-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010036030 Polyarthritis Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 108700033844 Pseudomonas aeruginosa toxA Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910052768 actinide Inorganic materials 0.000 description 1
- 150000001255 actinides Chemical class 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229960001391 alfentanil Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 208000037738 autosomal recessive channelopathy-associated congenital insensitivity to pain Diseases 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- JCXGWMGPZLAOME-AKLPVKDBSA-N bismuth-212 Chemical compound [212Bi] JCXGWMGPZLAOME-AKLPVKDBSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229960001736 buprenorphine Drugs 0.000 description 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 1
- IFKLAQQSCNILHL-QHAWAJNXSA-N butorphanol Chemical compound N1([C@@H]2CC3=CC=C(C=C3[C@@]3([C@]2(CCCC3)O)CC1)O)CC1CCC1 IFKLAQQSCNILHL-QHAWAJNXSA-N 0.000 description 1
- 229960001113 butorphanol Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000023135 chemokine (C-C motif) ligand 4 production Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- XLJKHNWPARRRJB-UHFFFAOYSA-N cobalt(2+) Chemical group [Co+2] XLJKHNWPARRRJB-UHFFFAOYSA-N 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000012866 crystallographic experiment Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 229960004193 dextropropoxyphene Drugs 0.000 description 1
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- 229960000920 dihydrocodeine Drugs 0.000 description 1
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 229960002428 fentanyl Drugs 0.000 description 1
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000012921 fluorescence analysis Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000000245 forearm Anatomy 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000037584 hereditary sensory and autonomic neuropathy Diseases 0.000 description 1
- 201000000887 hereditary sensory and autonomic neuropathy type 5 Diseases 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 102000052292 human CCL4 Human genes 0.000 description 1
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 description 1
- 229960000240 hydrocodone Drugs 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 description 1
- 229960001410 hydromorphone Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 208000021731 hypoalgesia Diseases 0.000 description 1
- 230000036032 hypoalgesia Effects 0.000 description 1
- 208000034783 hypoesthesia Diseases 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000006749 inflammatory damage Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 230000009191 jumping Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229960003406 levorphanol Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 210000001352 masseter muscle Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229960001797 methadone Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000019735 mitochondria-nucleus signaling pathway Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- NETZHAKZCGBWSS-CEDHKZHLSA-N nalbuphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@@H]3O)CN2CC1CCC1 NETZHAKZCGBWSS-CEDHKZHLSA-N 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 210000000929 nociceptor Anatomy 0.000 description 1
- 108091008700 nociceptors Proteins 0.000 description 1
- 229940121367 non-opioid analgesics Drugs 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229960005118 oxymorphone Drugs 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
- 229960005301 pentazocine Drugs 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 229960000482 pethidine Drugs 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 108700028325 pokeweed antiviral Proteins 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- REQCZEXYDRLIBE-UHFFFAOYSA-N procainamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(N)C=C1 REQCZEXYDRLIBE-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000011421 subcutaneous treatment Methods 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- GGCSSNBKKAUURC-UHFFFAOYSA-N sufentanil Chemical compound C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 GGCSSNBKKAUURC-UHFFFAOYSA-N 0.000 description 1
- 229960004739 sufentanil Drugs 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229910052713 technetium Inorganic materials 0.000 description 1
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
- Y02E50/00—Technologies for the production of fuel of non-fossil origin
- Y02E50/10—Biofuels, e.g. bio-diesel
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
- Y02E50/00—Technologies for the production of fuel of non-fossil origin
- Y02E50/30—Fuel from waste, e.g. synthetic alcohol or diesel
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- AIDS & HIV (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Obesity (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Microbiology (AREA)
- Mycology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2599508P | 2008-02-04 | 2008-02-04 | |
| US61/025,995 | 2008-02-04 | ||
| PCT/EP2009/051285 WO2009098238A1 (en) | 2008-02-04 | 2009-02-04 | Anti-trka antibodies and derivatives thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011514314A JP2011514314A (ja) | 2011-05-06 |
| JP2011514314A5 JP2011514314A5 (enExample) | 2012-03-15 |
| JP5719596B2 true JP5719596B2 (ja) | 2015-05-20 |
Family
ID=40521960
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010544733A Expired - Fee Related JP5719596B2 (ja) | 2008-02-04 | 2009-02-04 | 抗体及びその誘導体 |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US9751947B2 (enExample) |
| EP (1) | EP2252633B9 (enExample) |
| JP (1) | JP5719596B2 (enExample) |
| KR (1) | KR101782857B1 (enExample) |
| CN (1) | CN101939337B (enExample) |
| AP (1) | AP2929A (enExample) |
| AU (1) | AU2009211340B2 (enExample) |
| BR (1) | BRPI0905955A8 (enExample) |
| CA (1) | CA2713786A1 (enExample) |
| DK (1) | DK2252633T3 (enExample) |
| EA (1) | EA021284B1 (enExample) |
| ES (1) | ES2435917T3 (enExample) |
| IL (1) | IL207390A (enExample) |
| MX (1) | MX2010008571A (enExample) |
| MY (1) | MY191348A (enExample) |
| NZ (1) | NZ587701A (enExample) |
| PL (1) | PL2252633T3 (enExample) |
| PT (1) | PT2252633E (enExample) |
| WO (1) | WO2009098238A1 (enExample) |
| ZA (1) | ZA201006218B (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1306704B1 (it) | 1999-05-26 | 2001-10-02 | Sirs Societa Italiana Per La R | Anticorpi monoclonali e suoi derivati sintetici o biotecnologici ingrado di agire come molecole antagoniste per il ngf. |
| ITRM20050290A1 (it) | 2005-06-07 | 2006-12-08 | Lay Line Genomics Spa | Uso di molecole in grado di inibire il legame tra ngf e il suo recettore trka come analgesici ad effetto prolungato. |
| ITRM20050332A1 (it) | 2005-06-24 | 2006-12-25 | Lay Line Genomics Spa | Uso di molecole in grado di bloccare l'attivita' di trka per potenziare gli effetti di analgesici oppiacei sul dolore. |
| CA2713786A1 (en) | 2008-02-04 | 2009-08-13 | Lay Line Genomics S.P.A. | Anti-trka antibodies and antigen-binding derivatives thereof |
| WO2010029497A1 (en) * | 2008-09-12 | 2010-03-18 | Pfizer Limited | Treatment of endometriosis |
| EP3434691A1 (en) | 2010-12-01 | 2019-01-30 | AlderBio Holdings LLC | Anti-ngf compositions and use thereof |
| US9078878B2 (en) | 2010-12-01 | 2015-07-14 | Alderbio Holdings Llc | Anti-NGF antibodies that selectively inhibit the association of NGF with TrkA, without affecting the association of NGF with p75 |
| US9067988B2 (en) | 2010-12-01 | 2015-06-30 | Alderbio Holdings Llc | Methods of preventing or treating pain using anti-NGF antibodies |
| US11214610B2 (en) | 2010-12-01 | 2022-01-04 | H. Lundbeck A/S | High-purity production of multi-subunit proteins such as antibodies in transformed microbes such as Pichia pastoris |
| US9884909B2 (en) | 2010-12-01 | 2018-02-06 | Alderbio Holdings Llc | Anti-NGF compositions and use thereof |
| US9539324B2 (en) | 2010-12-01 | 2017-01-10 | Alderbio Holdings, Llc | Methods of preventing inflammation and treating pain using anti-NGF compositions |
| US20150183885A1 (en) * | 2012-06-08 | 2015-07-02 | Glenmark Pharmaceuticals S.A. | Anti-trka antibodies with enhanced inhibitory properties and derivatives thereof |
| UA113879C2 (xx) * | 2012-06-08 | 2017-03-27 | ГУМАНІЗОВАНЕ АНТИТІЛО ПРОТИ ТrkА З АМІНОКИСЛОТНИМИ ЗАМІЩЕННЯМИ | |
| EP2674439B1 (en) | 2012-06-13 | 2017-02-01 | Rottapharm Biotech S.r.l. | Anti-TrkA antibodies, derivatives and uses thereof |
| MA41097A (fr) * | 2014-12-05 | 2017-10-10 | Glenmark Pharmaceuticals Sa | Anticorps anti-trka à propriétés inhibitrices améliorées et dérivés desdits anticorps destinés à être utilisés pour traiter les douleurs osseuses |
| US10793634B2 (en) * | 2017-06-09 | 2020-10-06 | Boehringer Ingelheim International Gmbh | Anti-TrkB antibodies |
| AR114110A1 (es) | 2018-02-28 | 2020-07-22 | Lilly Co Eli | Anticuerpo anti-trka |
| CN109628425A (zh) * | 2019-01-02 | 2019-04-16 | 周越 | 一种人原肌球蛋白受体激酶a突变体及应用 |
| CN114230663B (zh) * | 2019-05-30 | 2022-09-27 | 广东东阳光药业有限公司 | TrkA的抗体及其应用 |
| WO2021092482A1 (en) * | 2019-11-06 | 2021-05-14 | The Regents Of The University Of California | Compositions and methods for transferrin receptor 1 targeting |
| EP4247852A4 (en) * | 2020-11-20 | 2024-10-23 | Sunshine Lake Pharma Co., Ltd. | HUMANIZED ANTI-TRKA ANTIBODIES AND USES THEREOF |
| CN117264068A (zh) | 2021-02-28 | 2023-12-22 | 熙源安健医药（上海）有限公司 | 抗TrkA抗体或其抗原结合片段、其制备方法和应用 |
| WO2023125490A1 (en) * | 2021-12-28 | 2023-07-06 | 4B Technologies (Suzhou) Limited | TrkA ANTIBODY AND APPLICATION THEREOF |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| US5530101A (en) * | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US6491916B1 (en) | 1994-06-01 | 2002-12-10 | Tolerance Therapeutics, Inc. | Methods and materials for modulation of the immunosuppresive activity and toxicity of monoclonal antibodies |
| GB9525180D0 (en) | 1995-12-08 | 1996-02-07 | Univ Mcgill | Design of hormone-like antibodies with agonistic and antagonistic fuctions |
| AU6956698A (en) | 1997-04-10 | 1998-10-30 | Genetics Institute Inc. | Secreted expressed sequence tags (sests) |
| US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
| GB2340334B (en) * | 1998-07-29 | 2003-06-25 | Ericsson Telefon Ab L M | Telephone apparatus |
| IT1306704B1 (it) * | 1999-05-26 | 2001-10-02 | Sirs Societa Italiana Per La R | Anticorpi monoclonali e suoi derivati sintetici o biotecnologici ingrado di agire come molecole antagoniste per il ngf. |
| FR2807660A1 (fr) | 2000-04-13 | 2001-10-19 | Warner Lambert Co | Utilisation d'antagonistes du ngf pour la prevention ou le traitement de douleurs viscerales chroniques |
| ES2357948T3 (es) | 2002-10-08 | 2011-05-04 | Rinat Neuroscience Corp. | Procedimientos para tratar dolor postquirúrgico mediante la administración de un anticuerpo frente al factor de crecimiento nervioso y composiciones que contienen el mismo. |
| UA80447C2 (en) | 2002-10-08 | 2007-09-25 | Methods for treating pain by administering nerve growth factor antagonist and opioid analgesic | |
| WO2005000194A2 (en) | 2002-10-08 | 2005-01-06 | Rinat Neuroscience Corp. | Methods for treating post-surgical pain by administering an anti-nerve growth factor antagonist antibody and compositions containing the same |
| ITRM20030601A1 (it) | 2003-12-24 | 2005-06-25 | Lay Line Genomics Spa | Metodo per l'umanizzazione di anticorpi e anticorpi umanizzati con esso ottenuti. |
| DK2206728T3 (en) | 2004-04-07 | 2018-04-23 | Rinat Neuroscience Corp | METHODS OF TREATING BONE CANCER PAIN BY SUBMITTING A NERVOUS FACTOR-ANTAGONISTIC ANTIBODY |
| ITRM20050290A1 (it) * | 2005-06-07 | 2006-12-08 | Lay Line Genomics Spa | Uso di molecole in grado di inibire il legame tra ngf e il suo recettore trka come analgesici ad effetto prolungato. |
| ITRM20050332A1 (it) * | 2005-06-24 | 2006-12-25 | Lay Line Genomics Spa | Uso di molecole in grado di bloccare l'attivita' di trka per potenziare gli effetti di analgesici oppiacei sul dolore. |
| CA2713786A1 (en) | 2008-02-04 | 2009-08-13 | Lay Line Genomics S.P.A. | Anti-trka antibodies and antigen-binding derivatives thereof |
| EP2732823B1 (en) | 2008-06-25 | 2019-08-07 | H. Lundbeck A/S | Modulation of the TrpV : Vps10p-domain receptor system for the treatment of pain |
-
2009
- 2009-02-04 CA CA2713786A patent/CA2713786A1/en not_active Abandoned
- 2009-02-04 NZ NZ587701A patent/NZ587701A/xx not_active IP Right Cessation
- 2009-02-04 BR BRPI0905955A patent/BRPI0905955A8/pt not_active Application Discontinuation
- 2009-02-04 MY MYPI2010003574A patent/MY191348A/en unknown
- 2009-02-04 EA EA201070888A patent/EA021284B1/ru unknown
- 2009-02-04 EP EP09708019.6A patent/EP2252633B9/en active Active
- 2009-02-04 PT PT97080196T patent/PT2252633E/pt unknown
- 2009-02-04 PL PL09708019T patent/PL2252633T3/pl unknown
- 2009-02-04 US US12/866,184 patent/US9751947B2/en not_active Expired - Fee Related
- 2009-02-04 DK DK09708019.6T patent/DK2252633T3/da active
- 2009-02-04 WO PCT/EP2009/051285 patent/WO2009098238A1/en not_active Ceased
- 2009-02-04 AP AP2010005379A patent/AP2929A/xx active
- 2009-02-04 CN CN200980104123.7A patent/CN101939337B/zh not_active Expired - Fee Related
- 2009-02-04 MX MX2010008571A patent/MX2010008571A/es active IP Right Grant
- 2009-02-04 AU AU2009211340A patent/AU2009211340B2/en not_active Ceased
- 2009-02-04 KR KR1020107019748A patent/KR101782857B1/ko not_active Expired - Fee Related
- 2009-02-04 ES ES09708019T patent/ES2435917T3/es active Active
- 2009-02-04 JP JP2010544733A patent/JP5719596B2/ja not_active Expired - Fee Related
-
2010
- 2010-08-03 IL IL207390A patent/IL207390A/en active IP Right Grant
- 2010-08-31 ZA ZA2010/06218A patent/ZA201006218B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0905955A2 (pt) | 2015-08-04 |
| AP2929A (en) | 2014-06-30 |
| IL207390A (en) | 2015-06-30 |
| AP2010005379A0 (en) | 2010-08-31 |
| AU2009211340B2 (en) | 2013-09-12 |
| ZA201006218B (en) | 2011-08-31 |
| EP2252633B9 (en) | 2014-02-19 |
| CN101939337B (zh) | 2016-03-09 |
| ES2435917T9 (es) | 2014-04-02 |
| MX2010008571A (es) | 2010-12-02 |
| WO2009098238A1 (en) | 2009-08-13 |
| NZ587701A (en) | 2013-03-28 |
| IL207390A0 (en) | 2010-12-30 |
| KR101782857B1 (ko) | 2017-09-28 |
| MY191348A (en) | 2022-06-17 |
| CN101939337A (zh) | 2011-01-05 |
| AU2009211340A1 (en) | 2009-08-13 |
| PT2252633E (pt) | 2013-11-19 |
| US20110145941A1 (en) | 2011-06-16 |
| BRPI0905955A8 (pt) | 2018-05-08 |
| EA021284B1 (ru) | 2015-05-29 |
| EP2252633A1 (en) | 2010-11-24 |
| CA2713786A1 (en) | 2009-08-13 |
| HK1150314A1 (en) | 2011-11-25 |
| EP2252633B1 (en) | 2013-08-14 |
| DK2252633T3 (da) | 2013-11-11 |
| ES2435917T3 (es) | 2013-12-26 |
| US9751947B2 (en) | 2017-09-05 |
| JP2011514314A (ja) | 2011-05-06 |
| KR20100114536A (ko) | 2010-10-25 |
| PL2252633T3 (pl) | 2014-02-28 |
| EA201070888A1 (ru) | 2011-04-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5719596B2 (ja) | 抗体及びその誘導体 | |
| JP7373650B2 (ja) | 抗ｐｄ－ｌ１シングルドメイン抗体 | |
| WO2016023001A1 (en) | Multispecific high affinity pd-1 agents and methods of use | |
| JP7539834B2 (ja) | ガレクチン－３に対する抗体及びその使用方法 | |
| KR20190002644A (ko) | FcγRIIA에 특이적인 결합 분자 및 이의 용도 | |
| JP2022523710A (ja) | Ｃｄ４４に特異的な抗体 | |
| US20220411520A1 (en) | Gipr antibody and fusion protein between same and glp-1, and pharmaceutical composition and application thereof | |
| US11780916B2 (en) | GIPR antibody and GLP-1 fusion protein thereof, and pharmaceutical composition and application thereof | |
| US11542336B2 (en) | GCGR antibody and GLP-1 fusion protein thereof, pharmaceutical composition thereof and application thereof | |
| KR20220092859A (ko) | 항-cxcr2 항체 및 이의 용도 | |
| KR20250027598A (ko) | Klrb1 결합제 및 이의 사용 방법 | |
| CN107614524A (zh) | 治疗 | |
| HK1150314B (en) | Anti-trka antibodies and derivatives thereof | |
| OA18848A (en) | Anti - TRKA antibodies and derivatives thereof. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120130 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120130 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131120 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140214 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140221 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140313 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140910 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150107 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20150107 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20150130 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150225 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150323 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5719596 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |