CA2944712A1 - Anti-factor d antibody variants and uses thereof - Google Patents
Anti-factor d antibody variants and uses thereof Download PDFInfo
- Publication number
- CA2944712A1 CA2944712A1 CA2944712A CA2944712A CA2944712A1 CA 2944712 A1 CA2944712 A1 CA 2944712A1 CA 2944712 A CA2944712 A CA 2944712A CA 2944712 A CA2944712 A CA 2944712A CA 2944712 A1 CA2944712 A1 CA 2944712A1
- Authority
- CA
- Canada
- Prior art keywords
- antibody
- factor
- seq
- sequence
- hvr
- 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.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 claims abstract description 97
- 239000003814 drug Substances 0.000 claims abstract description 49
- 238000011282 treatment Methods 0.000 claims abstract description 34
- 238000004519 manufacturing process Methods 0.000 claims abstract description 16
- 230000027455 binding Effects 0.000 claims description 103
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 86
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 68
- 230000000295 complement effect Effects 0.000 claims description 64
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 62
- 238000006467 substitution reaction Methods 0.000 claims description 55
- 208000002780 macular degeneration Diseases 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 49
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 41
- 238000009472 formulation Methods 0.000 claims description 41
- 208000005590 Choroidal Neovascularization Diseases 0.000 claims description 39
- 206010060823 Choroidal neovascularisation Diseases 0.000 claims description 39
- 208000008069 Geographic Atrophy Diseases 0.000 claims description 35
- 208000035475 disorder Diseases 0.000 claims description 35
- 230000001225 therapeutic effect Effects 0.000 claims description 33
- 239000005557 antagonist Substances 0.000 claims description 32
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 claims description 31
- 235000001014 amino acid Nutrition 0.000 claims description 31
- 238000006317 isomerization reaction Methods 0.000 claims description 30
- 125000000539 amino acid group Chemical group 0.000 claims description 29
- 230000006240 deamidation Effects 0.000 claims description 27
- 150000001875 compounds Chemical class 0.000 claims description 24
- 229940024606 amino acid Drugs 0.000 claims description 23
- 238000012384 transportation and delivery Methods 0.000 claims description 23
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 19
- -1 His Chemical compound 0.000 claims description 18
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 17
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 16
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 208000022873 Ocular disease Diseases 0.000 claims description 11
- 102100021119 Serine protease HTRA1 Human genes 0.000 claims description 11
- 206010046851 Uveitis Diseases 0.000 claims description 11
- 101001041393 Homo sapiens Serine protease HTRA1 Proteins 0.000 claims description 10
- 201000005667 central retinal vein occlusion Diseases 0.000 claims description 10
- 208000004644 retinal vein occlusion Diseases 0.000 claims description 10
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 9
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 8
- 229960001230 asparagine Drugs 0.000 claims description 8
- 235000009582 asparagine Nutrition 0.000 claims description 8
- 230000002035 prolonged effect Effects 0.000 claims description 8
- 101000666856 Homo sapiens Vasoactive intestinal polypeptide receptor 1 Proteins 0.000 claims description 7
- 102100038388 Vasoactive intestinal polypeptide receptor 1 Human genes 0.000 claims description 7
- 238000012216 screening Methods 0.000 claims description 6
- 206010055665 Corneal neovascularisation Diseases 0.000 claims description 5
- 206010012688 Diabetic retinal oedema Diseases 0.000 claims description 5
- 201000002563 Histoplasmosis Diseases 0.000 claims description 5
- 208000007135 Retinal Neovascularization Diseases 0.000 claims description 5
- 235000003704 aspartic acid Nutrition 0.000 claims description 5
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 5
- 201000000159 corneal neovascularization Diseases 0.000 claims description 5
- 208000001309 degenerative myopia Diseases 0.000 claims description 5
- 230000004340 degenerative myopia Effects 0.000 claims description 5
- 201000011190 diabetic macular edema Diseases 0.000 claims description 5
- 208000006542 von Hippel-Lindau disease Diseases 0.000 claims description 5
- 235000013922 glutamic acid Nutrition 0.000 claims description 4
- 239000004220 glutamic acid Substances 0.000 claims description 4
- FRYULLIZUDQONW-IMJSIDKUSA-N Asp-Asp Chemical group OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O FRYULLIZUDQONW-IMJSIDKUSA-N 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 125000003607 serino group Chemical class [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims 1
- 230000024203 complement activation Effects 0.000 abstract description 39
- 238000002360 preparation method Methods 0.000 abstract description 5
- 208000037765 diseases and disorders Diseases 0.000 abstract 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 87
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 87
- 230000037361 pathway Effects 0.000 description 59
- 235000018102 proteins Nutrition 0.000 description 55
- 102000004169 proteins and genes Human genes 0.000 description 55
- 108090000623 proteins and genes Proteins 0.000 description 55
- 239000000427 antigen Substances 0.000 description 51
- 108091007433 antigens Proteins 0.000 description 51
- 102000036639 antigens Human genes 0.000 description 51
- 206010018910 Haemolysis Diseases 0.000 description 49
- 230000008588 hemolysis Effects 0.000 description 49
- 239000002953 phosphate buffered saline Substances 0.000 description 47
- 239000012634 fragment Substances 0.000 description 45
- 229920000642 polymer Polymers 0.000 description 33
- 229940079593 drug Drugs 0.000 description 30
- 239000000872 buffer Substances 0.000 description 28
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 27
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 27
- 201000010099 disease Diseases 0.000 description 27
- 238000002347 injection Methods 0.000 description 27
- 239000007924 injection Substances 0.000 description 27
- 238000003556 assay Methods 0.000 description 26
- 239000000243 solution Substances 0.000 description 23
- 230000000694 effects Effects 0.000 description 22
- 208000011325 dry age related macular degeneration Diseases 0.000 description 21
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 18
- 108060003951 Immunoglobulin Proteins 0.000 description 18
- 102000018358 immunoglobulin Human genes 0.000 description 18
- 150000001413 amino acids Chemical class 0.000 description 17
- 230000004071 biological effect Effects 0.000 description 17
- 108090000765 processed proteins & peptides Proteins 0.000 description 17
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 16
- 230000004048 modification Effects 0.000 description 16
- 238000012986 modification Methods 0.000 description 16
- 238000011534 incubation Methods 0.000 description 15
- 238000005259 measurement Methods 0.000 description 15
- 229920001184 polypeptide Polymers 0.000 description 15
- 102000004196 processed proteins & peptides Human genes 0.000 description 15
- 150000003839 salts Chemical class 0.000 description 15
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 14
- 230000002776 aggregation Effects 0.000 description 14
- 238000004220 aggregation Methods 0.000 description 14
- 235000018417 cysteine Nutrition 0.000 description 13
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 210000001525 retina Anatomy 0.000 description 12
- 238000001542 size-exclusion chromatography Methods 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 108091006629 SLC13A2 Proteins 0.000 description 11
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 11
- 102220198533 rs1057520077 Human genes 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 241000124008 Mammalia Species 0.000 description 10
- 241000283973 Oryctolagus cuniculus Species 0.000 description 10
- 239000002202 Polyethylene glycol Substances 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 10
- 229920001223 polyethylene glycol Polymers 0.000 description 10
- 229960003876 ranibizumab Drugs 0.000 description 10
- 102220122856 rs201556985 Human genes 0.000 description 10
- 238000005119 centrifugation Methods 0.000 description 9
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 208000028867 ischemia Diseases 0.000 description 9
- 239000000178 monomer Substances 0.000 description 9
- 239000008188 pellet Substances 0.000 description 9
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 9
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 8
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 8
- 230000002378 acidificating effect Effects 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 229960003767 alanine Drugs 0.000 description 8
- 235000004279 alanine Nutrition 0.000 description 8
- 230000021615 conjugation Effects 0.000 description 8
- 238000000502 dialysis Methods 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 230000013595 glycosylation Effects 0.000 description 8
- 238000006206 glycosylation reaction Methods 0.000 description 8
- 230000002265 prevention Effects 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 238000003745 diagnosis Methods 0.000 description 7
- 238000012377 drug delivery Methods 0.000 description 7
- 230000005847 immunogenicity Effects 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 238000003780 insertion Methods 0.000 description 7
- 230000037431 insertion Effects 0.000 description 7
- 238000004255 ion exchange chromatography Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 230000007935 neutral effect Effects 0.000 description 7
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 7
- 230000002207 retinal effect Effects 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- 230000004304 visual acuity Effects 0.000 description 7
- 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 6
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 6
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 6
- 229920001213 Polysorbate 20 Polymers 0.000 description 6
- 230000004075 alteration Effects 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 206010014801 endophthalmitis Diseases 0.000 description 6
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 6
- 235000004554 glutamine Nutrition 0.000 description 6
- 229960002743 glutamine Drugs 0.000 description 6
- 229940072221 immunoglobulins Drugs 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 230000007170 pathology Effects 0.000 description 6
- 230000006320 pegylation Effects 0.000 description 6
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 239000003381 stabilizer Substances 0.000 description 6
- 125000003396 thiol group Chemical group [H]S* 0.000 description 6
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 5
- 208000023275 Autoimmune disease Diseases 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 5
- 241000283984 Rodentia Species 0.000 description 5
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 5
- 229940098773 bovine serum albumin Drugs 0.000 description 5
- 238000013270 controlled release Methods 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 229930182817 methionine Natural products 0.000 description 5
- 235000006109 methionine Nutrition 0.000 description 5
- 230000036515 potency Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 229940043131 pyroglutamate Drugs 0.000 description 5
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 4
- 206010002199 Anaphylactic shock Diseases 0.000 description 4
- 208000028185 Angioedema Diseases 0.000 description 4
- 201000004569 Blindness Diseases 0.000 description 4
- 241001146702 Candidatus Entotheonella factor Species 0.000 description 4
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 4
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 4
- 206010038923 Retinopathy Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000004473 Threonine Substances 0.000 description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 4
- 208000003455 anaphylaxis Diseases 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000002612 cardiopulmonary effect Effects 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 229960002989 glutamic acid Drugs 0.000 description 4
- 229960002449 glycine Drugs 0.000 description 4
- 238000001631 haemodialysis Methods 0.000 description 4
- 230000000322 hemodialysis Effects 0.000 description 4
- 229960002885 histidine Drugs 0.000 description 4
- 235000014304 histidine Nutrition 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 238000012506 imaged capillary isoelectric focusing Methods 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 230000004968 inflammatory condition Effects 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 229950000482 lampalizumab Drugs 0.000 description 4
- 108010032674 lampalizumab Proteins 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 4
- 239000003094 microcapsule Substances 0.000 description 4
- 201000006417 multiple sclerosis Diseases 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 206010028417 myasthenia gravis Diseases 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 150000005846 sugar alcohols Chemical class 0.000 description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000004393 visual impairment Effects 0.000 description 4
- OOIBFPKQHULHSQ-UHFFFAOYSA-N (3-hydroxy-1-adamantyl) 2-methylprop-2-enoate Chemical compound C1C(C2)CC3CC2(O)CC1(OC(=O)C(=C)C)C3 OOIBFPKQHULHSQ-UHFFFAOYSA-N 0.000 description 3
- 206010061623 Adverse drug reaction Diseases 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- 206010002329 Aneurysm Diseases 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- 206010066973 Contrast media allergy Diseases 0.000 description 3
- 208000011231 Crohn disease Diseases 0.000 description 3
- 208000025962 Crush injury Diseases 0.000 description 3
- 206010013700 Drug hypersensitivity Diseases 0.000 description 3
- 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 3
- 208000037487 Endotoxemia Diseases 0.000 description 3
- 208000032456 Hemorrhagic Shock Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 102000000588 Interleukin-2 Human genes 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 206010022680 Intestinal ischaemia Diseases 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- 206010025421 Macule Diseases 0.000 description 3
- 208000034486 Multi-organ failure Diseases 0.000 description 3
- 208000010718 Multiple Organ Failure Diseases 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 206010033645 Pancreatitis Diseases 0.000 description 3
- 206010036303 Post streptococcal glomerulonephritis Diseases 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- 206010040070 Septic Shock Diseases 0.000 description 3
- 206010049771 Shock haemorrhagic Diseases 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 206010052779 Transplant rejections Diseases 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 238000011481 absorbance measurement Methods 0.000 description 3
- 206010000891 acute myocardial infarction Diseases 0.000 description 3
- 201000005638 acute proliferative glomerulonephritis Diseases 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 229960003121 arginine Drugs 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000006172 buffering agent Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 150000001720 carbohydrates Chemical group 0.000 description 3
- 238000002144 chemical decomposition reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 230000036425 denaturation Effects 0.000 description 3
- 238000004925 denaturation Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 201000005311 drug allergy Diseases 0.000 description 3
- 238000013467 fragmentation Methods 0.000 description 3
- 238000006062 fragmentation reaction Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 229960003136 leucine Drugs 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 3
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 239000002736 nonionic surfactant Substances 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 230000036303 septic shock Effects 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 208000007056 sickle cell anemia Diseases 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 210000004127 vitreous body Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 2
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 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 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- 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 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 108010000817 Leuprolide Proteins 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 150000001408 amides Chemical group 0.000 description 2
- 229940124691 antibody therapeutics Drugs 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 210000001742 aqueous humor Anatomy 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- 229940009098 aspartate Drugs 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 239000008228 bacteriostatic water for injection Substances 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000007975 buffered saline Substances 0.000 description 2
- 239000004067 bulking agent Substances 0.000 description 2
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 238000001311 chemical methods and process Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000004154 complement system Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000001945 cysteines Chemical class 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 230000002327 eosinophilic effect Effects 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 239000005038 ethylene vinyl acetate Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000013265 extended release Methods 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000002949 hemolytic effect Effects 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- 229920001600 hydrophobic polymer Polymers 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000008676 import Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000000527 lymphocytic effect Effects 0.000 description 2
- 229960003646 lysine Drugs 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 230000003448 neutrophilic effect Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 108091008695 photoreceptors Proteins 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 239000012146 running buffer Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- KYOYLUVYCHVYGC-BUOKYLHBSA-M sodium (E)-but-2-enedioic acid (E)-4-hydroxy-4-oxobut-2-enoate Chemical compound [Na+].OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C([O-])=O KYOYLUVYCHVYGC-BUOKYLHBSA-M 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- UPMFZISCCZSDND-JJKGCWMISA-M sodium gluconate Chemical compound [Na+].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O UPMFZISCCZSDND-JJKGCWMISA-M 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 description 2
- 238000011179 visual inspection Methods 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- XMQUEQJCYRFIQS-YFKPBYRVSA-N (2s)-2-amino-5-ethoxy-5-oxopentanoic acid Chemical compound CCOC(=O)CC[C@H](N)C(O)=O XMQUEQJCYRFIQS-YFKPBYRVSA-N 0.000 description 1
- KYBXNPIASYUWLN-WUCPZUCCSA-N (2s)-5-hydroxypyrrolidine-2-carboxylic acid Chemical compound OC1CC[C@@H](C(O)=O)N1 KYBXNPIASYUWLN-WUCPZUCCSA-N 0.000 description 1
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- BFUUJUGQJUTPAF-UHFFFAOYSA-N 2-(3-amino-4-propoxybenzoyl)oxyethyl-diethylazanium;chloride Chemical compound [Cl-].CCCOC1=CC=C(C(=O)OCC[NH+](CC)CC)C=C1N BFUUJUGQJUTPAF-UHFFFAOYSA-N 0.000 description 1
- 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 description 1
- HTCSFFGLRQDZDE-UHFFFAOYSA-N 2-azaniumyl-2-phenylpropanoate Chemical compound OC(=O)C(N)(C)C1=CC=CC=C1 HTCSFFGLRQDZDE-UHFFFAOYSA-N 0.000 description 1
- XBBVURRQGJPTHH-UHFFFAOYSA-N 2-hydroxyacetic acid;2-hydroxypropanoic acid Chemical compound OCC(O)=O.CC(O)C(O)=O XBBVURRQGJPTHH-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- 229940117976 5-hydroxylysine Drugs 0.000 description 1
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102220473488 Alpha-1B-glycoprotein_D32S_mutation Human genes 0.000 description 1
- 108010003529 Alternative Pathway Complement C3 Convertase Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108010089414 Anaphylatoxins Proteins 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 108090000056 Complement factor B Proteins 0.000 description 1
- 102000003712 Complement factor B Human genes 0.000 description 1
- 102100034622 Complement factor B Human genes 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- HEBKCHPVOIAQTA-QWWZWVQMSA-N D-arabinitol Chemical compound OC[C@@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-QWWZWVQMSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- LLQPHQFNMLZJMP-UHFFFAOYSA-N Fentrazamide Chemical compound N1=NN(C=2C(=CC=CC=2)Cl)C(=O)N1C(=O)N(CC)C1CCCCC1 LLQPHQFNMLZJMP-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 206010018370 Glomerulonephritis membranoproliferative Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 101150007028 HTRA1 gene Proteins 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 1
- 208000024781 Immune Complex disease Diseases 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 238000012695 Interfacial polymerization Methods 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- 239000004395 L-leucine Substances 0.000 description 1
- 235000019454 L-leucine Nutrition 0.000 description 1
- 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 208000005777 Lupus Nephritis Diseases 0.000 description 1
- 239000006137 Luria-Bertani broth Substances 0.000 description 1
- 239000004907 Macro-emulsion Substances 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 208000004451 Membranoproliferative Glomerulonephritis Diseases 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000282339 Mustela Species 0.000 description 1
- 208000007201 Myocardial reperfusion injury Diseases 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 108091060545 Nonsense suppressor Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 206010057430 Retinal injury Diseases 0.000 description 1
- JVWLUVNSQYXYBE-UHFFFAOYSA-N Ribitol Natural products OCC(C)C(O)C(O)CO JVWLUVNSQYXYBE-UHFFFAOYSA-N 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- UQZIYBXSHAGNOE-USOSMYMVSA-N Stachyose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](CO[C@@H]2[C@@H](O)[C@@H](O)[C@@H](O)[C@H](CO)O2)O1 UQZIYBXSHAGNOE-USOSMYMVSA-N 0.000 description 1
- 229920002472 Starch Polymers 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 102100038968 WAP four-disulfide core domain protein 1 Human genes 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- GZLGNNHEHXBCBI-UHFFFAOYSA-L [Na+].[Na+].OC(=O)C(O)C(O)C(O)=O.[O-]C(=O)C(O)C(O)C([O-])=O Chemical compound [Na+].[Na+].OC(=O)C(O)C(O)C(O)=O.[O-]C(=O)C(O)C(O)C([O-])=O GZLGNNHEHXBCBI-UHFFFAOYSA-L 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 229940087458 alcaine Drugs 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940125644 antibody drug Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 238000011190 asparagine deamidation Methods 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 210000004191 axillary artery Anatomy 0.000 description 1
- 229960002319 barbital Drugs 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- HUTDDBSSHVOYJR-UHFFFAOYSA-H bis[(2-oxo-1,3,2$l^{5},4$l^{2}-dioxaphosphaplumbetan-2-yl)oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O HUTDDBSSHVOYJR-UHFFFAOYSA-H 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 230000008993 bowel inflammation Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000012219 cassette mutagenesis Methods 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 201000002388 complement deficiency Diseases 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 150000003999 cyclitols Chemical class 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 239000008380 degradant Substances 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- KNKDZWFHOIKECV-UHFFFAOYSA-L dipotassium 2,3,4-trihydroxy-4-oxobutanoate Chemical compound [K+].[K+].OC(=O)C(O)C(O)C(O)=O.[O-]C(=O)C(O)C(O)C([O-])=O KNKDZWFHOIKECV-UHFFFAOYSA-L 0.000 description 1
- OQOQSRMIBLJVHE-UHFFFAOYSA-L dipotassium 2-hydroxy-2-oxoacetate Chemical compound [K+].[K+].OC(=O)C(O)=O.[O-]C(=O)C([O-])=O OQOQSRMIBLJVHE-UHFFFAOYSA-L 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- WGFMTHGYKYEDHF-UHFFFAOYSA-L disodium 2-hydroxy-2-oxoacetate Chemical compound [Na+].[Na+].OC(=O)C(O)=O.[O-]C(=O)C([O-])=O WGFMTHGYKYEDHF-UHFFFAOYSA-L 0.000 description 1
- SILCDLWESNHZKB-UHFFFAOYSA-L disodium 4-hydroxy-4-oxobutanoate Chemical compound [Na+].[Na+].OC(=O)CCC([O-])=O.OC(=O)CCC([O-])=O SILCDLWESNHZKB-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- MYSDBRXBYJKGLB-WOGKQDBSSA-L disodium;(e)-but-2-enedioate;(e)-but-2-enedioic acid Chemical compound [Na+].[Na+].OC(=O)\C=C\C(O)=O.[O-]C(=O)\C=C\C([O-])=O MYSDBRXBYJKGLB-WOGKQDBSSA-L 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 239000011536 extraction buffer Substances 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000013534 fluorescein angiography Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000005350 fused silica glass Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229940127022 high-dose drug Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 238000009474 hot melt extrusion Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 229940050526 hydroxyethylstarch Drugs 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 230000004377 improving vision Effects 0.000 description 1
- 238000009540 indirect ophthalmoscopy Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000011268 leukocyte chemotaxis Effects 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229940087857 lupron Drugs 0.000 description 1
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940100630 metacresol Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229940111688 monobasic potassium phosphate Drugs 0.000 description 1
- 239000012514 monoclonal antibody product Substances 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 108091005763 multidomain proteins Proteins 0.000 description 1
- 230000002911 mydriatic effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 230000031978 negative regulation of complement activation Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000013631 noncovalent dimer Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 108010054442 polyalanine Chemical group 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000006267 polysialylation Effects 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LCPMNMXCIHBTEX-UHFFFAOYSA-M potassium;2-hydroxypropanoate;2-hydroxypropanoic acid Chemical compound [K+].CC(O)C(O)=O.CC(O)C([O-])=O LCPMNMXCIHBTEX-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000009163 protein therapy Methods 0.000 description 1
- 230000010344 pupil dilation Effects 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- HEBKCHPVOIAQTA-ZXFHETKHSA-N ribitol Chemical compound OC[C@H](O)[C@H](O)[C@H](O)CO HEBKCHPVOIAQTA-ZXFHETKHSA-N 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 102220068344 rs199989979 Human genes 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- GNBVPFITFYNRCN-UHFFFAOYSA-M sodium thioglycolate Chemical compound [Na+].[O-]C(=O)CS GNBVPFITFYNRCN-UHFFFAOYSA-M 0.000 description 1
- 229940046307 sodium thioglycolate Drugs 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 229940001474 sodium thiosulfate Drugs 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- LLVQEXSQFBTIRD-UHFFFAOYSA-M sodium;2,3,4-trihydroxy-4-oxobutanoate;hydrate Chemical compound O.[Na+].OC(=O)C(O)C(O)C([O-])=O LLVQEXSQFBTIRD-UHFFFAOYSA-M 0.000 description 1
- KMPHTYSTEHXSTL-UHFFFAOYSA-M sodium;2-hydroxypropanoate;2-hydroxypropanoic acid Chemical compound [Na+].CC(O)C(O)=O.CC(O)C([O-])=O KMPHTYSTEHXSTL-UHFFFAOYSA-M 0.000 description 1
- VDZDAHYKYRVHJR-UHFFFAOYSA-M sodium;2-hydroxypropanoate;hydrate Chemical compound [OH-].[Na+].CC(O)C(O)=O VDZDAHYKYRVHJR-UHFFFAOYSA-M 0.000 description 1
- OESFSXYRSCBAQJ-UHFFFAOYSA-M sodium;3-carboxy-3,5-dihydroxy-5-oxopentanoate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.OC(=O)CC(O)(C(O)=O)CC([O-])=O OESFSXYRSCBAQJ-UHFFFAOYSA-M 0.000 description 1
- DGPIGKCOQYBCJH-UHFFFAOYSA-M sodium;acetic acid;hydroxide Chemical compound O.[Na+].CC([O-])=O DGPIGKCOQYBCJH-UHFFFAOYSA-M 0.000 description 1
- VBGUQBPWJMPQBI-UHFFFAOYSA-M sodium;butanedioic acid;4-hydroxy-4-oxobutanoate Chemical compound [Na+].OC(=O)CCC(O)=O.OC(=O)CCC([O-])=O VBGUQBPWJMPQBI-UHFFFAOYSA-M 0.000 description 1
- JISIBLCXFLGVJX-UHFFFAOYSA-M sodium;butanedioic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)CCC(O)=O JISIBLCXFLGVJX-UHFFFAOYSA-M 0.000 description 1
- KIJIBEBWNNLSKE-UHFFFAOYSA-M sodium;oxalic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)C(O)=O KIJIBEBWNNLSKE-UHFFFAOYSA-M 0.000 description 1
- UQZIYBXSHAGNOE-XNSRJBNMSA-N stachyose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)O2)O)O1 UQZIYBXSHAGNOE-XNSRJBNMSA-N 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000008362 succinate buffer Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000008646 thermal stress Effects 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 229940035024 thioglycerol Drugs 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 229960000707 tobramycin Drugs 0.000 description 1
- NLVFBUXFDBBNBW-PBSUHMDJSA-S tobramycin(5+) Chemical compound [NH3+][C@@H]1C[C@H](O)[C@@H](C[NH3+])O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H]([NH3+])[C@H](O)[C@@H](CO)O2)O)[C@H]([NH3+])C[C@@H]1[NH3+] NLVFBUXFDBBNBW-PBSUHMDJSA-S 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229940126672 traditional medicines Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- JYXKLAOSCQDVIX-NFMYELBMSA-K trisodium (E)-but-2-enedioate (E)-4-hydroxy-4-oxobut-2-enoate Chemical compound [Na+].[Na+].[Na+].OC(=O)\C=C\C([O-])=O.[O-]C(=O)\C=C\C([O-])=O JYXKLAOSCQDVIX-NFMYELBMSA-K 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229960004791 tropicamide Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229940045136 urea Drugs 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 230000007998 vessel formation Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- 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
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21046—Complement factor D (3.4.21.46)
-
- 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
- C07K2317/55—Fab or Fab'
-
- 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
-
- 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
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Ophthalmology & Optometry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- General Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Urology & Nephrology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461987298P | 2014-05-01 | 2014-05-01 | |
| US61/987,298 | 2014-05-01 | ||
| US201462076372P | 2014-11-06 | 2014-11-06 | |
| US62/076,372 | 2014-11-06 | ||
| PCT/US2015/028641 WO2015168468A1 (en) | 2014-05-01 | 2015-04-30 | Anti-factor d antibody variants and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2944712A1 true CA2944712A1 (en) | 2015-11-05 |
Family
ID=53059539
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2944712A Abandoned CA2944712A1 (en) | 2014-05-01 | 2015-04-30 | Anti-factor d antibody variants and uses thereof |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US10179821B2 (enExample) |
| EP (1) | EP3137503A1 (enExample) |
| JP (1) | JP2017515811A (enExample) |
| KR (1) | KR20160147855A (enExample) |
| CN (1) | CN106536561A (enExample) |
| AU (1) | AU2015253042A1 (enExample) |
| BR (1) | BR112016025312A2 (enExample) |
| CA (1) | CA2944712A1 (enExample) |
| CL (1) | CL2016002738A1 (enExample) |
| CR (1) | CR20160561A (enExample) |
| EA (1) | EA201692109A1 (enExample) |
| IL (1) | IL248042A0 (enExample) |
| MA (1) | MA39934A (enExample) |
| MX (1) | MX2016014160A (enExample) |
| PE (1) | PE20161440A1 (enExample) |
| PH (1) | PH12016502015A1 (enExample) |
| SG (1) | SG11201608868PA (enExample) |
| TW (1) | TW201623337A (enExample) |
| WO (1) | WO2015168468A1 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10093978B2 (en) | 2013-08-12 | 2018-10-09 | Genentech, Inc. | Compositions for detecting complement factor H (CFH) and complement factor I (CFI) polymorphisms |
| MA39934A (fr) | 2014-05-01 | 2017-03-08 | Hoffmann La Roche | Variants d'anticorps anti-facteur d et leurs utilisations |
| US9840553B2 (en) | 2014-06-28 | 2017-12-12 | Kodiak Sciences Inc. | Dual PDGF/VEGF antagonists |
| WO2017075173A2 (en) * | 2015-10-30 | 2017-05-04 | Genentech, Inc. | Anti-factor d antibodies and conjugates |
| WO2017075252A1 (en) * | 2015-10-30 | 2017-05-04 | Genentech, Inc. | Anti-factor d antibody variant conjugates and uses thereof |
| CA3003647A1 (en) * | 2015-10-30 | 2017-05-04 | Genentech, Inc. | Anti-factor d antibody formulations |
| WO2017117464A1 (en) | 2015-12-30 | 2017-07-06 | Kodiak Sciences Inc. | Antibodies and conjugates thereof |
| GB2553252B (en) * | 2016-01-20 | 2019-07-31 | Vitrisa Therapeutics Inc | Aptamers that block the catalytic cleft of complement Factor D |
| CN107043422B (zh) * | 2016-01-28 | 2022-01-04 | 成都康弘生物科技有限公司 | 抗补体因子D的人源化Fab和人源化抗体及其用途 |
| WO2018136827A1 (en) | 2017-01-20 | 2018-07-26 | Vitrisa Therapeutics, Inc. | Stem-loop compositions and methods for inhibiting factor d |
| IL268601B2 (en) * | 2017-02-10 | 2024-07-01 | Univ Pennsylvania | Anti-factor d antibodies and uses thereof |
| CN106905431B (zh) * | 2017-04-10 | 2020-01-17 | 旭华（上海）生物研发中心有限公司 | 抗人补体d因子的单克隆抗体及其用途 |
| WO2018191548A2 (en) | 2017-04-14 | 2018-10-18 | Kodiak Sciences Inc. | Complement factor d antagonist antibodies and conjugates thereof |
| CA3157509A1 (en) | 2019-10-10 | 2021-04-15 | Kodiak Sciences Inc. | Methods of treating an eye disorder |
| CN115666578A (zh) | 2020-05-12 | 2023-01-31 | 阿雷克森制药公司 | 补体因子d抑制剂单独或结合抗c5抗体治疗阵发性睡眠性血红蛋白尿的用途 |
| WO2022133169A1 (en) | 2020-12-18 | 2022-06-23 | Century Therapeutics, Inc. | Chimeric antigen receptor systems with adaptable receptor specificity |
| JP2024515066A (ja) * | 2021-04-09 | 2024-04-04 | 武田薬品工業株式会社 | 補体因子ｄを標的とする抗体及びその使用 |
| WO2025045250A1 (en) * | 2023-09-03 | 2025-03-06 | Kira Pharmaceuticals (Us) Llc | Anti-human factor d antibody constructs and uses thereof |
| WO2025199107A1 (en) | 2024-03-19 | 2025-09-25 | Alexion Pharmaceuticals, Inc. | Risk evaluation and management strategy involving patient follow-ups relating to the use or discontinuation of a complement inhibitor |
Family Cites Families (150)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4741900A (en) | 1982-11-16 | 1988-05-03 | Cytogen Corporation | Antibody-metal ion complexes |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| GB8430252D0 (en) | 1984-11-30 | 1985-01-09 | Beecham Group Plc | Compounds |
| US5206344A (en) | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| EP0245993B1 (en) | 1986-04-28 | 1993-05-26 | Cetus Oncology Corporation | Monoclonal antibodies against c5a and des-arg74-c5a, their production and use |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5256642A (en) | 1988-04-01 | 1993-10-26 | The Johns Hopkins University | Compositions of soluble complement receptor 1 (CR1) and a thrombolytic agent, and the methods of use thereof |
| NZ230747A (en) | 1988-09-30 | 1992-05-26 | Bror Morein | Immunomodulating matrix comprising a complex of at least one lipid and at least one saponin; certain glycosylated triterpenoid saponins derived from quillaja saponaria molina |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5166322A (en) | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| US5244800A (en) | 1990-04-27 | 1993-09-14 | The Uab Research Foundation | Crystals of human complement factor d that are triclinic |
| US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
| JP4124480B2 (ja) | 1991-06-14 | 2008-07-23 | ジェネンテック・インコーポレーテッド | 免疫グロブリン変異体 |
| WO1993000109A1 (en) | 1991-06-28 | 1993-01-07 | Genentech, Inc. | Method of stimulating immune response using growth hormone |
| FI941572L (fi) | 1991-10-07 | 1994-05-27 | Oncologix Inc | Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenetelmä |
| AU675929B2 (en) | 1992-02-06 | 1997-02-27 | Curis, Inc. | Biosynthetic binding protein for cancer marker |
| US5456909A (en) | 1992-08-07 | 1995-10-10 | T Cell Sciences, Inc. | Glycoform fractions of recombinant soluble complement receptor 1 (sCR1) having extended half-lives in vivo |
| ZA936128B (en) | 1992-08-21 | 1995-02-20 | Genentech Inc | Method for treating a LFA-1 mediated disorder |
| CA2149048A1 (en) | 1992-11-25 | 1994-06-09 | George N. Cox | Modified insulin-like growth factors |
| US5861156A (en) | 1993-01-08 | 1999-01-19 | Creative Biomolecules | Methods of delivering agents to target cells |
| CN1134111A (zh) | 1993-04-07 | 1996-10-23 | 赛纳根公司 | 使用胰岛素样生长因子结合蛋白质的方法 |
| US5856300A (en) | 1994-05-12 | 1999-01-05 | T Cell Sciences, Inc. | Compositions comprising complement related proteins and carbohydrates, and methods for producing and using said compositions |
| US5849535A (en) | 1995-09-21 | 1998-12-15 | Genentech, Inc. | Human growth hormone variants |
| US5679546A (en) | 1993-09-24 | 1997-10-21 | Cytomed, Inc. | Chimeric proteins which block complement activation |
| US5627264A (en) | 1994-03-03 | 1997-05-06 | Alexion Pharmaceuticals, Inc. | Chimeric complement inhibitor proteins |
| EP0751787B1 (en) | 1994-03-23 | 2005-01-12 | Alexion Pharmaceuticals, Inc. | Method for reducing immune and hemostatic dysfunctions during extracorporeal circulation |
| US5534615A (en) | 1994-04-25 | 1996-07-09 | Genentech, Inc. | Cardiac hypertrophy factor and uses therefor |
| US5919623A (en) | 1994-04-27 | 1999-07-06 | St. James's And Seacroft University Hospitals Nhs Trust | Nucleic acid mutation assays |
| US6074642A (en) | 1994-05-02 | 2000-06-13 | Alexion Pharmaceuticals, Inc. | Use of antibodies specific to human complement component C5 for the treatment of glomerulonephritis |
| US5679345A (en) | 1994-06-02 | 1997-10-21 | The Johns Hopkins University | Method for preventing complement-dependent rejection of organ or tissue transplants |
| WO2001004311A1 (en) | 1999-07-07 | 2001-01-18 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| US5897475A (en) | 1994-10-05 | 1999-04-27 | Antex Biologics, Inc. | Vaccines comprising enhanced antigenic helicobacter spp. |
| US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
| US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| WO2002000690A2 (en) | 2000-06-23 | 2002-01-03 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis |
| WO1999046281A2 (en) | 1998-03-10 | 1999-09-16 | Genentech, Inc. | Novel polypeptides and nucleic acids encoding the same |
| WO2002008284A2 (en) | 2000-07-20 | 2002-01-31 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis |
| US7122636B1 (en) | 1997-02-21 | 2006-10-17 | Genentech, Inc. | Antibody fragment-polymer conjugates and uses of same |
| US20050197285A1 (en) | 1997-03-07 | 2005-09-08 | Rosen Craig A. | Human secreted proteins |
| US6472520B2 (en) | 1997-03-21 | 2002-10-29 | The Trustees Of Columbia University In The City Of New York | Rat PEG-3 promoter |
| BRPI9809387B8 (pt) | 1997-04-07 | 2021-05-25 | Genentech Inc | anticorpo humanizado anti-fator de crescimento endotelial vascular humano e composição que o compreende |
| US6884879B1 (en) | 1997-04-07 | 2005-04-26 | Genentech, Inc. | Anti-VEGF antibodies |
| US5994511A (en) | 1997-07-02 | 1999-11-30 | Genentech, Inc. | Anti-IgE antibodies and methods of improving polypeptides |
| DE69838552T2 (de) | 1997-07-14 | 2008-05-21 | Bolder Biotechnology, Inc., Louisville | Derivate des wachstumshormons und verwandte proteine |
| US6410708B1 (en) | 1997-11-21 | 2002-06-25 | Genentech, Inc. | Nucleic acids encoding A-33 related antigen polypeptides |
| DE69835524T2 (de) | 1997-08-26 | 2007-04-05 | Amgen Fremont Inc. | Ein verfahren zur inhibierung der komplementaktivierung über einen alternativen weg |
| US8007798B2 (en) | 1997-11-21 | 2011-08-30 | Genentech, Inc. | Treatment of complement-associated disorders |
| US8088386B2 (en) | 1998-03-20 | 2012-01-03 | Genentech, Inc. | Treatment of complement-associated disorders |
| US7419663B2 (en) | 1998-03-20 | 2008-09-02 | Genentech, Inc. | Treatment of complement-associated disorders |
| EP2014677A1 (en) | 1997-11-21 | 2009-01-14 | Genentech, Inc. | A-33 related antigens and their pharmacological uses |
| US7282565B2 (en) | 1998-03-20 | 2007-10-16 | Genentech, Inc. | PRO362 polypeptides |
| US7192589B2 (en) | 1998-09-16 | 2007-03-20 | Genentech, Inc. | Treatment of inflammatory disorders with STIgMA immunoadhesins |
| US7005504B2 (en) | 1998-01-22 | 2006-02-28 | Genentech, Inc. | Antibody fragment-peg conjugates |
| EP1053245A4 (en) | 1998-02-09 | 2002-04-17 | Human Genome Sciences Inc | 45 HUMAN SECRETED PROTEINS |
| US6956107B2 (en) | 1998-02-20 | 2005-10-18 | Tanox, Inc. | Inhibitors of complement activation |
| US7112327B2 (en) | 1998-02-20 | 2006-09-26 | Tanox, Inc. | Inhibition of complement activation |
| EP1054693B8 (en) | 1998-02-20 | 2009-03-04 | Genentech, Inc. | Inhibitors of complement activation |
| EP1108019A2 (en) | 1998-08-27 | 2001-06-20 | Incyte Pharmaceuticals, Inc. | Protein transport-associated molecules |
| US6376653B1 (en) | 1998-09-28 | 2002-04-23 | Smithkline Beecham Plc | Tie2 antagonist antibodies |
| KR100468977B1 (ko) | 1998-12-16 | 2005-02-02 | 제넨테크, 인크. | 분비 및 막횡단 폴리펩티드, 및 이를 코딩하는 핵산 |
| EP1141284A2 (en) | 1998-12-22 | 2001-10-10 | Genentech, Inc. | Methods and compositions for inhibiting neoplastic cell growth |
| KR20060067983A (ko) | 1999-01-15 | 2006-06-20 | 제넨테크, 인크. | 효과기 기능이 변화된 폴리펩티드 변이체 |
| AU3514400A (en) | 1999-03-08 | 2000-09-28 | Genentech Inc. | Compositions and methods for the treatment of immune related diseases |
| EP2292761A1 (en) | 1999-03-11 | 2011-03-09 | Merck Serono S.A. | Vascular adhesion molecules and modulation of their function |
| US6642353B1 (en) | 1999-03-17 | 2003-11-04 | Chugai Seiyaku Kabushiki Kaisha | Peptide ligands for the erythropoietin receptor |
| EP1234030A4 (en) | 1999-11-19 | 2003-05-07 | Human Genome Sciences Inc | 18 HUMAN SECRETED PROTEINS |
| CA2490853A1 (en) | 1999-12-01 | 2001-06-07 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| EP1253946A2 (en) | 2000-02-10 | 2002-11-06 | Alexion Pharmaceuticals, Inc. | Mixtures of caspase inhibitors and complement inhibitors and methods of use thereof |
| US6821775B1 (en) | 2000-02-11 | 2004-11-23 | Genvec, Inc. | Viral vector encoding pigment epithelium-derived factor |
| ES2329010T3 (es) | 2000-03-23 | 2009-11-20 | Genentech, Inc. | Inhibidores anti-c2/c2a de la activacion del complemento. |
| EP2026073B1 (en) | 2000-04-29 | 2016-03-30 | University Of Iowa Research Foundation | Diagnostics and therapeutics for macular degeneration-related disorders |
| ES2333775T3 (es) | 2000-10-10 | 2010-03-01 | Genentech, Inc. | Inhibicion de la activacion del complemento c5 para el tratamiento y la prevencion de rechazo de xenoinjerto retrasado o rechazo vascular agudo. |
| US6875432B2 (en) | 2000-10-12 | 2005-04-05 | Genentech, Inc. | Reduced-viscosity concentrated protein formulations |
| JP2004532608A (ja) | 2000-10-13 | 2004-10-28 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | ヒト化抗ＬＴ−β−Ｒ抗体 |
| CA2433353C (en) | 2000-12-28 | 2017-03-21 | Altus Biologics, Inc. | Crystals of whole antibodies and fragments thereof and methods for making and using them |
| US20040077575A1 (en) | 2002-01-11 | 2004-04-22 | Giordano Giovan Giacomo | Inhibition of pathological angiogenesis in vivo |
| US6867189B2 (en) | 2001-07-26 | 2005-03-15 | Genset S.A. | Use of adipsin/complement factor D in the treatment of metabolic related disorders |
| MXPA04001301A (es) | 2001-08-17 | 2004-07-08 | Tanox Inc | Inhibidores de la ruta del complemento que se unen a c5 y c5a son evitar la formacion de c5b. |
| US20040186051A1 (en) | 2001-10-02 | 2004-09-23 | Kelley Robert F | Apo-2 ligand variants and uses thereof |
| US20060141561A1 (en) | 2002-06-24 | 2006-06-29 | Kelley Robert F | Apo-2 ligand/trail variants and uses thereof |
| EP1575514A2 (en) | 2002-07-31 | 2005-09-21 | Seattle Genetics, Inc. | Anti-cd20 antibody-drug conjugates for the treatment of cancer and immune disorders |
| TWI323265B (en) | 2002-08-06 | 2010-04-11 | Glaxo Group Ltd | Antibodies |
| US20040152105A1 (en) | 2002-09-06 | 2004-08-05 | Cytos Biotechnology Ag. | Immune modulatory compounds and methods |
| US7816497B2 (en) | 2002-10-30 | 2010-10-19 | University Of Kentucky | Compositions and methods for inhibiting drusen complement components C3a and C5a for the treatment of age-related macular degeneration |
| AU2003301813A1 (en) | 2002-10-30 | 2004-06-07 | University Of Kentucky Research Foundation | Methods and animal model for analyzing age-related macular degeneration |
| MXPA05008570A (es) | 2003-02-21 | 2005-11-04 | Tanox Inc | Metodos para la prevencion y tratamiento de danos tisulares asociados con una lesion por isquemia-reperfusion. |
| RU2232991C1 (ru) | 2003-04-09 | 2004-07-20 | Государственное учреждение "Московский научно-исследовательский институт эпидемиологии и микробиологии им. Г.Н. Габричевского" | Способ определения функциональной активности фактора d комплемента человека |
| KR100512483B1 (ko) | 2003-05-07 | 2005-09-05 | 선바이오(주) | 신규한 폴리에틸렌글리콜-말레이미드 유도체의 합성방법 |
| US7709610B2 (en) | 2003-05-08 | 2010-05-04 | Facet Biotech Corporation | Therapeutic use of anti-CS1 antibodies |
| EP2267028A3 (en) | 2003-06-30 | 2011-07-27 | Domantis Limited | Dual specific single domain antibodies (dAb) conjugated to PEG |
| WO2005014849A2 (en) | 2003-07-03 | 2005-02-17 | Euro-Celtique, S.A. | Genes associated with responses to neuropathic pain |
| US20050106667A1 (en) | 2003-08-01 | 2005-05-19 | Genentech, Inc | Binding polypeptides with restricted diversity sequences |
| WO2005044853A2 (en) | 2003-11-01 | 2005-05-19 | Genentech, Inc. | Anti-vegf antibodies |
| WO2005025509A2 (en) | 2003-09-11 | 2005-03-24 | Board Of Regents, The University Of Texas System | Methods and materials for treating autoimmune diseases and conditions |
| US20050169921A1 (en) | 2004-02-03 | 2005-08-04 | Leonard Bell | Method of treating hemolytic disease |
| US7127355B2 (en) | 2004-03-05 | 2006-10-24 | Perlegen Sciences, Inc. | Methods for genetic analysis |
| US20090087854A1 (en) | 2007-09-27 | 2009-04-02 | Perlegen Sciences, Inc. | Methods for genetic analysis |
| US7794713B2 (en) | 2004-04-07 | 2010-09-14 | Lpath, Inc. | Compositions and methods for the treatment and prevention of hyperproliferative diseases |
| CN104447992A (zh) | 2004-09-23 | 2015-03-25 | 健泰科生物技术公司 | 半胱氨酸改造的抗体和偶联物 |
| ATE528410T1 (de) | 2004-11-18 | 2011-10-15 | Univ Yale | Verfahren und zusammensetzungen zur diagnose von altersbedingter maculadegeneration |
| WO2006071856A2 (en) | 2004-12-23 | 2006-07-06 | Glycofi, Inc. | Immunoglobulins comprising predominantly a man5glcnac2 glycoform |
| JP5068175B2 (ja) | 2005-01-04 | 2012-11-07 | 日立化成工業株式会社 | プライマー生成ローリングサークル型増幅 |
| MX2007009565A (es) | 2005-02-14 | 2008-03-10 | Univ Iowa Res Found | Metodos y reactivos para tratamiento y diagnostico de degeneracion macular relacionada con la edad. |
| JP5620058B2 (ja) | 2005-06-08 | 2014-11-05 | ユニバーシティ オブ ピッツバーグ オブ ザ コモンウェルス システム オブ ハイヤー エデュケイション | 染色体１０ｑ２６上の加齢性黄斑変性症（ＡＲＭ）に対する感受性遺伝子 |
| AU2006302212B2 (en) | 2005-10-08 | 2012-12-20 | Apellis Pharmaceuticals, Inc. | Compstatin and analogs thereof for eye disorders |
| KR20150055628A (ko) | 2005-11-04 | 2015-05-21 | 제넨테크, 인크. | 안질환 치료를 위한 보체 경로 억제제의 용도 |
| US20070190057A1 (en) | 2006-01-23 | 2007-08-16 | Jian Wu | Methods for modulating mannose content of recombinant proteins |
| AR059066A1 (es) | 2006-01-27 | 2008-03-12 | Amgen Inc | Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf) |
| US20080146501A1 (en) | 2006-02-13 | 2008-06-19 | University Of Iowa Research Foundation | Protective complement proteins and age-related macular degeneration |
| EP2004643A1 (en) | 2006-03-31 | 2008-12-24 | Novartis AG | Organic compounds |
| PT2944306T (pt) | 2006-06-16 | 2021-02-15 | Regeneron Pharma | Formulações antagonistas de vegf adequadas para administração intravitreal |
| CN101541345A (zh) * | 2006-09-25 | 2009-09-23 | 米迪缪尼有限公司 | 稳定化的抗体制剂和其应用 |
| KR20090060453A (ko) * | 2006-09-25 | 2009-06-12 | 메디뮨 엘엘씨 | 안정화된 항체 제제 및 그것의 용도 |
| DK2097455T3 (en) | 2006-11-02 | 2014-12-15 | Genentech Inc | HUMANIZED ANTI-FACTOR D ANTIBODIES |
| CA2705500A1 (en) | 2007-05-11 | 2008-11-20 | Tufts Medical Center | Polynucleotides associated with age-related macular degeneration and methods for evaluating patient risk |
| AR066660A1 (es) | 2007-05-23 | 2009-09-02 | Genentech Inc | Prevencion y tratamiento de condiciones del ojo asociadas con su complemento |
| RU2481355C2 (ru) * | 2007-05-24 | 2013-05-10 | Аблинкс Н.В. | Аминокислотные последовательности, направленные на rank-l, и полипептиды, включающие их, для лечения заболеваний и нарушений костей |
| US20090203001A1 (en) | 2007-08-24 | 2009-08-13 | The Regents Of The University Of Michigan | Compositions and methods for diagnosing and treating macular degeneration |
| WO2009146204A1 (en) | 2008-04-18 | 2009-12-03 | Tufts Medical Center | Polymorphisms associated with age-related macular degeneration and methods for evaluating patient risk |
| CR20170001A (es) | 2008-04-28 | 2017-08-10 | Genentech Inc | Anticuerpos anti factor d humanizados |
| WO2009134709A2 (en) | 2008-04-28 | 2009-11-05 | Tufts Medical Center | Polynucleotides associated with age-related macular degeneration and methods for evaluating patient risk |
| PL2307455T3 (pl) | 2008-06-25 | 2017-09-29 | Esbatech, An Alcon Biomedical Research Unit Llc | Optymalizacja rozpuszczalności cząsteczek immunowiążących |
| CN101724144A (zh) | 2008-11-03 | 2010-06-09 | 北京键凯科技有限公司 | 新型的多臂聚乙二醇及其制备方法和应用 |
| WO2010054110A2 (en) | 2008-11-05 | 2010-05-14 | Genentech, Inc. | Genetic polymorphisms in age-related macular degeneration |
| US20120115925A1 (en) | 2008-12-23 | 2012-05-10 | Massachusetts Eye And Ear Infirmary | Allelic Variants Associated with Advanced Age-Related Macular Degeneration |
| MX2011006726A (es) | 2009-01-02 | 2011-07-20 | Alcon Res Ltd | Implante oftalmico recargable in situ. |
| WO2010085542A2 (en) | 2009-01-23 | 2010-07-29 | Novartis Ag | Biomarkers related to age-related macular degeneration (amd) |
| SG173167A1 (en) | 2009-01-29 | 2011-08-29 | Forsight Labs Llc | Posterior segment drug delivery |
| WO2010132459A2 (en) | 2009-05-11 | 2010-11-18 | Cleveland Clinic Foundation | Biomarkers for assessment of age-related macular degeneration |
| US20110212433A1 (en) | 2009-07-02 | 2011-09-01 | Lanza Tech New Zealand Limited | Alcohol production process |
| WO2011006161A2 (en) | 2009-07-10 | 2011-01-13 | The Regents Of The University Of Michigan | Compositions and methods for diagnosing and treating macular degeneration |
| WO2011017229A2 (en) | 2009-08-06 | 2011-02-10 | Tufts - New England Medical Center | Plasma complement components as expression markers for age-related macular degeneration and related phenotypes |
| US8221753B2 (en) * | 2009-09-30 | 2012-07-17 | Tracon Pharmaceuticals, Inc. | Endoglin antibodies |
| US20110165648A1 (en) | 2009-11-04 | 2011-07-07 | Menno Van Lookeren Campagne | Co-crystal structure of factor D and anti-factor D antibody |
| WO2011061119A1 (en) * | 2009-11-19 | 2011-05-26 | Merck Serono S.A. | Humanized antibodies against human il-22ra |
| CN107337734A (zh) | 2009-12-04 | 2017-11-10 | 弗·哈夫曼-拉罗切有限公司 | 多特异性抗体、抗体类似物、组合物和方法 |
| CN103755949B (zh) | 2009-12-25 | 2016-04-13 | 天津键凯科技有限公司 | 多臂聚乙二醇衍生物及其与药物的结合物和凝胶 |
| NZ608814A (en) * | 2010-09-03 | 2015-06-26 | Stem Centrx Inc | Novel modulators and methods of use |
| DK2635704T3 (en) | 2010-11-01 | 2017-06-19 | Hoffmann La Roche | Predicting progression to advanced age-related macular degeneration using a polygenic score |
| CN103619881B (zh) * | 2011-04-07 | 2017-07-28 | 安姆根有限公司 | 新的egfr结合蛋白 |
| MX390891B (es) | 2011-10-14 | 2025-03-19 | Genentech Inc | ANTICUERPOS ANTI-HtrA1 Y MÉTODOS DE USO. |
| TWI593705B (zh) * | 2011-12-28 | 2017-08-01 | Chugai Pharmaceutical Co Ltd | Humanized anti-epiregulin antibody and cancer therapeutic agent containing the antibody as an active ingredient |
| JP6051998B2 (ja) | 2012-03-30 | 2016-12-27 | 日油株式会社 | マルチアーム型ポリエチレングリコール誘導体、その中間体及び製造方法 |
| US10093978B2 (en) | 2013-08-12 | 2018-10-09 | Genentech, Inc. | Compositions for detecting complement factor H (CFH) and complement factor I (CFI) polymorphisms |
| JP6580570B2 (ja) * | 2013-09-06 | 2019-09-25 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 抗体安定性を向上させるための方法 |
| MA39934A (fr) | 2014-05-01 | 2017-03-08 | Hoffmann La Roche | Variants d'anticorps anti-facteur d et leurs utilisations |
-
2015
- 2015-04-30 MA MA039934A patent/MA39934A/fr unknown
- 2015-04-30 PE PE2016002153A patent/PE20161440A1/es not_active Application Discontinuation
- 2015-04-30 AU AU2015253042A patent/AU2015253042A1/en not_active Abandoned
- 2015-04-30 KR KR1020167032259A patent/KR20160147855A/ko not_active Withdrawn
- 2015-04-30 BR BR112016025312A patent/BR112016025312A2/pt not_active Application Discontinuation
- 2015-04-30 WO PCT/US2015/028641 patent/WO2015168468A1/en not_active Ceased
- 2015-04-30 SG SG11201608868PA patent/SG11201608868PA/en unknown
- 2015-04-30 JP JP2016564582A patent/JP2017515811A/ja active Pending
- 2015-04-30 TW TW104114014A patent/TW201623337A/zh unknown
- 2015-04-30 EA EA201692109A patent/EA201692109A1/ru unknown
- 2015-04-30 US US14/700,853 patent/US10179821B2/en not_active Expired - Fee Related
- 2015-04-30 CA CA2944712A patent/CA2944712A1/en not_active Abandoned
- 2015-04-30 MX MX2016014160A patent/MX2016014160A/es unknown
- 2015-04-30 CN CN201580023643.0A patent/CN106536561A/zh active Pending
- 2015-04-30 EP EP15721516.1A patent/EP3137503A1/en not_active Withdrawn
- 2015-04-30 CR CR20160561A patent/CR20160561A/es unknown
-
2016
- 2016-09-26 IL IL248042A patent/IL248042A0/en unknown
- 2016-10-10 PH PH12016502015A patent/PH12016502015A1/en unknown
- 2016-10-27 CL CL2016002738A patent/CL2016002738A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20160017052A1 (en) | 2016-01-21 |
| AU2015253042A1 (en) | 2016-10-20 |
| TW201623337A (zh) | 2016-07-01 |
| AU2015253042A2 (en) | 2016-10-27 |
| PE20161440A1 (es) | 2017-01-26 |
| CL2016002738A1 (es) | 2017-06-23 |
| EA201692109A1 (ru) | 2017-03-31 |
| PH12016502015A1 (en) | 2017-01-16 |
| US10179821B2 (en) | 2019-01-15 |
| MA39934A (fr) | 2017-03-08 |
| MX2016014160A (es) | 2017-02-16 |
| IL248042A0 (en) | 2016-11-30 |
| WO2015168468A1 (en) | 2015-11-05 |
| SG11201608868PA (en) | 2016-11-29 |
| CR20160561A (es) | 2017-05-03 |
| CN106536561A (zh) | 2017-03-22 |
| KR20160147855A (ko) | 2016-12-23 |
| BR112016025312A2 (pt) | 2017-10-17 |
| JP2017515811A (ja) | 2017-06-15 |
| EP3137503A1 (en) | 2017-03-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10179821B2 (en) | Anti-factor D antibodies | |
| JP7550251B2 (ja) | 糖尿病黄斑浮腫の治療のための組成物および方法 | |
| TWI616456B (zh) | 人類化之抗因子ｄ抗體及其用途 | |
| TWI472535B (zh) | 人類化之抗-因子ｄ抗體及其用途 | |
| US10961313B2 (en) | Anti-factor D antibody variant conjugates and uses thereof | |
| EP2831113B1 (en) | Antibodies to bradykinin b1 receptor ligands | |
| JP2018534930A (ja) | 抗ｄ因子抗体及びコンジュゲート | |
| HK1230624A1 (en) | Anti-factor d antibody variants and uses thereof | |
| OA17139A (en) | Antibodies to bradykinin B1 receptor ligands |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20200831 |