CA2992660A1 - Heavy chain only antibodies to ang-2 - Google Patents
Heavy chain only antibodies to ang-2 Download PDFInfo
- Publication number
- CA2992660A1 CA2992660A1 CA2992660A CA2992660A CA2992660A1 CA 2992660 A1 CA2992660 A1 CA 2992660A1 CA 2992660 A CA2992660 A CA 2992660A CA 2992660 A CA2992660 A CA 2992660A CA 2992660 A1 CA2992660 A1 CA 2992660A1
- Authority
- CA
- Canada
- Prior art keywords
- hcab
- ang
- antigen
- binding specificity
- antibody
- 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.)
- Pending
Links
- 230000027455 binding Effects 0.000 claims abstract description 80
- 102100034608 Angiopoietin-2 Human genes 0.000 claims abstract description 71
- 108010048036 Angiopoietin-2 Proteins 0.000 claims abstract description 69
- 239000000427 antigen Substances 0.000 claims abstract description 63
- 108091007433 antigens Proteins 0.000 claims abstract description 63
- 102000036639 antigens Human genes 0.000 claims abstract description 63
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims abstract description 23
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims abstract 2
- 150000001413 amino acids Chemical group 0.000 claims description 65
- 241000282414 Homo sapiens Species 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 53
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 22
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 208000005590 Choroidal Neovascularization Diseases 0.000 claims description 13
- 206010060823 Choroidal neovascularisation Diseases 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 206010012688 Diabetic retinal oedema Diseases 0.000 claims description 11
- 201000011190 diabetic macular edema Diseases 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 10
- 229960003876 ranibizumab Drugs 0.000 claims description 10
- 206010030113 Oedema Diseases 0.000 claims description 9
- 201000000159 corneal neovascularization Diseases 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 230000002159 abnormal effect Effects 0.000 claims description 8
- 229960000397 bevacizumab Drugs 0.000 claims description 8
- 208000001344 Macular Edema Diseases 0.000 claims description 5
- 206010025415 Macular oedema Diseases 0.000 claims description 5
- 206010025421 Macule Diseases 0.000 claims description 5
- 208000000208 Wet Macular Degeneration Diseases 0.000 claims description 5
- 201000010230 macular retinal edema Diseases 0.000 claims description 5
- 230000004379 myopia Effects 0.000 claims description 5
- 208000001491 myopia Diseases 0.000 claims description 5
- 208000004644 retinal vein occlusion Diseases 0.000 claims description 5
- 230000002792 vascular Effects 0.000 claims description 5
- 206010021143 Hypoxia Diseases 0.000 claims description 4
- 201000002154 Pterygium Diseases 0.000 claims description 4
- 206010038886 Retinal oedema Diseases 0.000 claims description 4
- 208000011325 dry age related macular degeneration Diseases 0.000 claims description 4
- 230000007954 hypoxia Effects 0.000 claims description 4
- 206010023332 keratitis Diseases 0.000 claims description 4
- 238000002054 transplantation Methods 0.000 claims description 4
- 210000004027 cell Anatomy 0.000 description 61
- 210000001508 eye Anatomy 0.000 description 54
- 235000001014 amino acid Nutrition 0.000 description 49
- 229940024606 amino acid Drugs 0.000 description 47
- 238000012377 drug delivery Methods 0.000 description 26
- 239000000203 mixture Substances 0.000 description 26
- 238000002347 injection Methods 0.000 description 25
- 239000007924 injection Substances 0.000 description 25
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 24
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 24
- 108090000623 proteins and genes Proteins 0.000 description 24
- 229920000642 polymer Polymers 0.000 description 22
- 238000006467 substitution reaction Methods 0.000 description 19
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 18
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 18
- 239000013543 active substance Substances 0.000 description 17
- 230000014509 gene expression Effects 0.000 description 16
- 239000007943 implant Substances 0.000 description 16
- 150000007523 nucleic acids Chemical class 0.000 description 15
- 108090000765 processed proteins & peptides Proteins 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- 206010064930 age-related macular degeneration Diseases 0.000 description 14
- 239000000017 hydrogel Substances 0.000 description 14
- 208000002780 macular degeneration Diseases 0.000 description 14
- 108020004707 nucleic acids Proteins 0.000 description 14
- 102000039446 nucleic acids Human genes 0.000 description 14
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- 108060003951 Immunoglobulin Proteins 0.000 description 13
- 230000006870 function Effects 0.000 description 13
- 102000018358 immunoglobulin Human genes 0.000 description 13
- 229920001184 polypeptide Polymers 0.000 description 13
- 235000018102 proteins Nutrition 0.000 description 13
- 108020004414 DNA Proteins 0.000 description 12
- -1 His Chemical compound 0.000 description 11
- 229920002988 biodegradable polymer Polymers 0.000 description 11
- 239000004621 biodegradable polymer Substances 0.000 description 11
- 230000004048 modification Effects 0.000 description 11
- 238000012986 modification Methods 0.000 description 11
- 239000013598 vector Substances 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 210000004204 blood vessel Anatomy 0.000 description 10
- 239000012634 fragment Substances 0.000 description 10
- 108010048154 Angiopoietin-1 Proteins 0.000 description 9
- 102100034594 Angiopoietin-1 Human genes 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 239000002245 particle Substances 0.000 description 9
- 239000008194 pharmaceutical composition Substances 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 230000013595 glycosylation Effects 0.000 description 8
- 238000006206 glycosylation reaction Methods 0.000 description 8
- 239000002502 liposome Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 7
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 7
- 229920001577 copolymer Polymers 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 238000013268 sustained release Methods 0.000 description 7
- 239000012730 sustained-release form Substances 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 206010012689 Diabetic retinopathy Diseases 0.000 description 6
- 101000924533 Homo sapiens Angiopoietin-2 Proteins 0.000 description 6
- 230000033115 angiogenesis Effects 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- 238000003780 insertion Methods 0.000 description 6
- 230000037431 insertion Effects 0.000 description 6
- 239000011159 matrix material Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 5
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- 201000004569 Blindness Diseases 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 5
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 5
- 238000012867 alanine scanning Methods 0.000 description 5
- 229940127089 cytotoxic agent Drugs 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 229920002674 hyaluronan Polymers 0.000 description 5
- 229960003160 hyaluronic acid Drugs 0.000 description 5
- 210000004408 hybridoma Anatomy 0.000 description 5
- 238000002513 implantation Methods 0.000 description 5
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 5
- 239000004005 microsphere Substances 0.000 description 5
- 229920000747 poly(lactic acid) Polymers 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 210000001525 retina Anatomy 0.000 description 5
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 102100033402 Angiopoietin-4 Human genes 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 4
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 4
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 4
- 102100038232 Vascular endothelial growth factor C Human genes 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 108010069801 angiopoietin 4 Proteins 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 230000001588 bifunctional effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000006172 buffering agent Substances 0.000 description 4
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 230000003628 erosive effect Effects 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 210000003292 kidney cell Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 4
- 238000002703 mutagenesis Methods 0.000 description 4
- 231100000350 mutagenesis Toxicity 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 3
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 206010029113 Neovascularisation Diseases 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 208000022873 Ocular disease Diseases 0.000 description 3
- 229920001244 Poly(D,L-lactide) Polymers 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 description 3
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 3
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 3
- 208000032594 Vascular Remodeling Diseases 0.000 description 3
- 102100038234 Vascular endothelial growth factor D Human genes 0.000 description 3
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 3
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 230000009824 affinity maturation Effects 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 150000001720 carbohydrates Chemical group 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000002254 cytotoxic agent Substances 0.000 description 3
- 231100000599 cytotoxic agent Toxicity 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000007951 isotonicity adjuster Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 229920001432 poly(L-lactide) Polymers 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- 108700012359 toxins Proteins 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000011830 transgenic mouse model Methods 0.000 description 3
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- VPFUWHKTPYPNGT-UHFFFAOYSA-N 3-(3,4-dihydroxyphenyl)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)propan-1-one Chemical compound OC1=C2C=CC(C)(C)OC2=CC=C1C(=O)CCC1=CC=C(O)C(O)=C1 VPFUWHKTPYPNGT-UHFFFAOYSA-N 0.000 description 2
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- 108010009906 Angiopoietins Proteins 0.000 description 2
- 102000009840 Angiopoietins Human genes 0.000 description 2
- 235000002198 Annona diversifolia Nutrition 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000282832 Camelidae Species 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 241000255925 Diptera Species 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 241001138401 Kluyveromyces lactis Species 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 241000282838 Lama Species 0.000 description 2
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 108010082093 Placenta Growth Factor Proteins 0.000 description 2
- 102100035194 Placenta growth factor Human genes 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 206010038848 Retinal detachment Diseases 0.000 description 2
- 241000607720 Serratia Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 241000256251 Spodoptera frugiperda Species 0.000 description 2
- 102000012753 TIE-2 Receptor Human genes 0.000 description 2
- 108010090091 TIE-2 Receptor Proteins 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000001745 anti-biotin effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229960004926 chlorobutanol Drugs 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 230000004438 eyesight Effects 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 229940127121 immunoconjugate Drugs 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 230000035168 lymphangiogenesis Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 2
- 229920001434 poly(D-lactide) Polymers 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 238000012667 polymer degradation Methods 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 229940068984 polyvinyl alcohol Drugs 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000004264 retinal detachment Effects 0.000 description 2
- 230000037390 scarring Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 230000004393 visual impairment Effects 0.000 description 2
- 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
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical class CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 description 1
- IEUUDEWWMRQUDS-UHFFFAOYSA-N (6-azaniumylidene-1,6-dimethoxyhexylidene)azanium;dichloride Chemical compound Cl.Cl.COC(=N)CCCCC(=N)OC IEUUDEWWMRQUDS-UHFFFAOYSA-N 0.000 description 1
- 229920003178 (lactide-co-glycolide) polymer Polymers 0.000 description 1
- JCIIKRHCWVHVFF-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine;hydrochloride Chemical compound Cl.NC1=NC=NS1 JCIIKRHCWVHVFF-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 1
- VILFTWLXLYIEMV-UHFFFAOYSA-N 1,5-difluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=C(F)C=C1F VILFTWLXLYIEMV-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- YBBNVCVOACOHIG-UHFFFAOYSA-N 2,2-diamino-1,4-bis(4-azidophenyl)-3-butylbutane-1,4-dione Chemical compound C=1C=C(N=[N+]=[N-])C=CC=1C(=O)C(N)(N)C(CCCC)C(=O)C1=CC=C(N=[N+]=[N-])C=C1 YBBNVCVOACOHIG-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FZDFGHZZPBUTGP-UHFFFAOYSA-N 2-[[2-[bis(carboxymethyl)amino]-3-(4-isothiocyanatophenyl)propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)C(C)CN(CC(O)=O)CC(N(CC(O)=O)CC(O)=O)CC1=CC=C(N=C=S)C=C1 FZDFGHZZPBUTGP-UHFFFAOYSA-N 0.000 description 1
- FBUTXZSKZCQABC-UHFFFAOYSA-N 2-amino-1-methyl-7h-purine-6-thione Chemical compound S=C1N(C)C(N)=NC2=C1NC=N2 FBUTXZSKZCQABC-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
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229940117976 5-hydroxylysine Drugs 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical class O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 108010066676 Abrin Proteins 0.000 description 1
- 241000256118 Aedes aegypti Species 0.000 description 1
- 241000256173 Aedes albopictus Species 0.000 description 1
- WQVFQXXBNHHPLX-ZKWXMUAHSA-N Ala-Ala-His Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O WQVFQXXBNHHPLX-ZKWXMUAHSA-N 0.000 description 1
- YYSWCHMLFJLLBJ-ZLUOBGJFSA-N Ala-Ala-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YYSWCHMLFJLLBJ-ZLUOBGJFSA-N 0.000 description 1
- IPWKGIFRRBGCJO-IMJSIDKUSA-N Ala-Ser Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](CO)C([O-])=O IPWKGIFRRBGCJO-IMJSIDKUSA-N 0.000 description 1
- PTNFNTOBUDWHNZ-GUBZILKMSA-N Asn-Arg-Met Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(O)=O PTNFNTOBUDWHNZ-GUBZILKMSA-N 0.000 description 1
- MECFLTFREHAZLH-ACZMJKKPSA-N Asn-Glu-Cys Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N MECFLTFREHAZLH-ACZMJKKPSA-N 0.000 description 1
- KHCNTVRVAYCPQE-CIUDSAMLSA-N Asn-Lys-Asn Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O KHCNTVRVAYCPQE-CIUDSAMLSA-N 0.000 description 1
- JHFNSBBHKSZXKB-VKHMYHEASA-N Asp-Gly Chemical compound OC(=O)C[C@H](N)C(=O)NCC(O)=O JHFNSBBHKSZXKB-VKHMYHEASA-N 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241000351920 Aspergillus nidulans Species 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 101000669426 Aspergillus restrictus Ribonuclease mitogillin Proteins 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 241001367049 Autographa Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 241000194108 Bacillus licheniformis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 108010081589 Becaplermin Proteins 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 241000255789 Bombyx mori Species 0.000 description 1
- 241000409811 Bombyx mori nucleopolyhedrovirus Species 0.000 description 1
- 108030001720 Bontoxilysin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 101710158575 Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Chemical class 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 108700032819 Croton tiglium crotin II Proteins 0.000 description 1
- 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 1
- 229930182843 D-Lactic acid Natural products 0.000 description 1
- 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 1
- 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 1
- JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 241000255601 Drosophila melanogaster Species 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 241000588698 Erwinia Species 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241001522878 Escherichia coli B Species 0.000 description 1
- 241001302584 Escherichia coli str. K-12 substr. W3110 Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 101710082714 Exotoxin A Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920002148 Gellan gum Polymers 0.000 description 1
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 208000008069 Geographic Atrophy Diseases 0.000 description 1
- YYOBUPFZLKQUAX-FXQIFTODSA-N Glu-Asn-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O YYOBUPFZLKQUAX-FXQIFTODSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 201000002563 Histoplasmosis Diseases 0.000 description 1
- 101000955962 Homo sapiens Vacuolar protein sorting-associated protein 51 homolog Proteins 0.000 description 1
- IOVUXUSIGXCREV-DKIMLUQUSA-N Ile-Leu-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 IOVUXUSIGXCREV-DKIMLUQUSA-N 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 102000016844 Immunoglobulin-like domains Human genes 0.000 description 1
- 108050006430 Immunoglobulin-like domains Proteins 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 241000235649 Kluyveromyces Species 0.000 description 1
- 244000285963 Kluyveromyces fragilis Species 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- 241000481961 Lachancea thermotolerans Species 0.000 description 1
- 241000235651 Lachancea waltii Species 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 244000302512 Momordica charantia Species 0.000 description 1
- 235000009811 Momordica charantia Nutrition 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- WTBIAPVQQBCLFP-UHFFFAOYSA-N N.N.N.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O Chemical compound N.N.N.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O WTBIAPVQQBCLFP-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000221960 Neurospora Species 0.000 description 1
- 241000221961 Neurospora crassa Species 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000034530 PLAA-associated neurodevelopmental disease Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000228143 Penicillium Species 0.000 description 1
- 240000007377 Petunia x hybrida Species 0.000 description 1
- WEMYTDDMDBLPMI-DKIMLUQUSA-N Phe-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N WEMYTDDMDBLPMI-DKIMLUQUSA-N 0.000 description 1
- KIQUCMUULDXTAZ-HJOGWXRNSA-N Phe-Tyr-Tyr Chemical compound N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(O)=O KIQUCMUULDXTAZ-HJOGWXRNSA-N 0.000 description 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 101100413173 Phytolacca americana PAP2 gene Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 102000001393 Platelet-Derived Growth Factor alpha Receptor Human genes 0.000 description 1
- 108010068588 Platelet-Derived Growth Factor alpha Receptor Proteins 0.000 description 1
- 102100037596 Platelet-derived growth factor subunit A Human genes 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920000805 Polyaspartic acid Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 101000732674 Rattus norvegicus Angiopoietin-2 Proteins 0.000 description 1
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000014139 Retinal vascular disease Diseases 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 241000235347 Schizosaccharomyces pombe Species 0.000 description 1
- 241000311088 Schwanniomyces Species 0.000 description 1
- 241001123650 Schwanniomyces occidentalis Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- QMCDMHWAKMUGJE-IHRRRGAJSA-N Ser-Phe-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O QMCDMHWAKMUGJE-IHRRRGAJSA-N 0.000 description 1
- DKGRNFUXVTYRAS-UBHSHLNASA-N Ser-Ser-Trp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O DKGRNFUXVTYRAS-UBHSHLNASA-N 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 241000255588 Tephritidae Species 0.000 description 1
- COYHRQWNJDJCNA-NUJDXYNKSA-N Thr-Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O COYHRQWNJDJCNA-NUJDXYNKSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 241001149964 Tolypocladium Species 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 241000223259 Trichoderma Species 0.000 description 1
- KHPLUFDSWGDRHD-SLFFLAALSA-N Tyr-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)N)C(=O)O KHPLUFDSWGDRHD-SLFFLAALSA-N 0.000 description 1
- 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 description 1
- 240000001866 Vernicia fordii Species 0.000 description 1
- 241000235013 Yarrowia Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 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
- 108010001818 alpha-sarcin Proteins 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 108010047857 aspartylglycine Proteins 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 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
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 238000012575 bio-layer interferometry Methods 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000004352 blood vessel remodeling Effects 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 210000001775 bruch membrane Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Chemical class 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Chemical class 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 238000012219 cassette mutagenesis Methods 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 201000005667 central retinal vein occlusion Diseases 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 238000011098 chromatofocusing Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 210000004240 ciliary body Anatomy 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000005289 controlled pore glass Substances 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229940022769 d- lactic acid Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000007857 degradation product 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
- 230000000994 depressogenic effect Effects 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 229930191339 dianthin Natural products 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 125000005442 diisocyanate group Chemical group 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- ZWIBGKZDAWNIFC-UHFFFAOYSA-N disuccinimidyl suberate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)CCC1=O ZWIBGKZDAWNIFC-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 108010028531 enomycin Proteins 0.000 description 1
- 229940116977 epidermal growth factor Drugs 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
- 150000002148 esters Chemical class 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229940014041 hyaluronate Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 208000018769 loss of vision Diseases 0.000 description 1
- 231100000864 loss of vision Toxicity 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 108010010621 modeccin Proteins 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000005157 neural retina Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 201000005111 ocular hyperemia Diseases 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000000059 patterning Methods 0.000 description 1
- 239000001814 pectin Chemical class 0.000 description 1
- 229920001277 pectin Chemical class 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229960000292 pectin Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 108010076042 phenomycin Proteins 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 229940096826 phenylmercuric acetate Drugs 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 108091008695 photoreceptors Proteins 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 108010000685 platelet-derived growth factor AB Proteins 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002239 polyacrylonitrile Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 108010054442 polyalanine Proteins 0.000 description 1
- 108010064470 polyaspartate Proteins 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 108700015048 receptor decoy activity proteins Proteins 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 210000001927 retinal artery Anatomy 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 201000003772 severe nonproliferative diabetic retinopathy Diseases 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229940100996 sodium bisulfate Drugs 0.000 description 1
- 229940001607 sodium bisulfite Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 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
- 235000010339 sodium tetraborate Nutrition 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
- 239000002904 solvent Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000012414 sterilization procedure Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 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
- 238000000108 ultra-filtration Methods 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 230000006426 vascular sprouting Effects 0.000 description 1
- 230000004862 vasculogenesis Effects 0.000 description 1
- 230000007998 vessel formation Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/522—CH1 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/526—CH3 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Ophthalmology & Optometry (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562198518P | 2015-07-29 | 2015-07-29 | |
| US62/198,518 | 2015-07-29 | ||
| US201562205185P | 2015-08-14 | 2015-08-14 | |
| US62/205,185 | 2015-08-14 | ||
| PCT/US2016/044838 WO2017020001A2 (en) | 2015-07-29 | 2016-07-29 | Heavy chain only antibodies to ang-2 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2992660A1 true CA2992660A1 (en) | 2017-02-02 |
Family
ID=56610025
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2992660A Pending CA2992660A1 (en) | 2015-07-29 | 2016-07-29 | Heavy chain only antibodies to ang-2 |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US10266589B2 (enExample) |
| EP (2) | EP3792279A3 (enExample) |
| JP (1) | JP6916776B2 (enExample) |
| CN (1) | CN107849126B (enExample) |
| AU (2) | AU2016298398A1 (enExample) |
| BR (1) | BR112018001762A2 (enExample) |
| CA (1) | CA2992660A1 (enExample) |
| DK (1) | DK3328886T3 (enExample) |
| ES (1) | ES2828694T3 (enExample) |
| HU (1) | HUE051165T2 (enExample) |
| PL (1) | PL3328886T3 (enExample) |
| RU (1) | RU2749674C2 (enExample) |
| WO (1) | WO2017020001A2 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12478503B2 (en) | 2009-05-18 | 2025-11-25 | Glaukos Corporation | Implants with controlled drug delivery features and methods of using same |
| US10206813B2 (en) | 2009-05-18 | 2019-02-19 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
| CN107849126B (zh) * | 2015-07-29 | 2022-04-08 | 阿勒根公司 | 仅有重链的抗ang-2抗体 |
| AU2016307943A1 (en) * | 2015-08-14 | 2018-02-15 | Allergan, Inc. | Heavy chain only antibodies to PDGF |
| US20220185875A1 (en) * | 2019-03-18 | 2022-06-16 | Jiangsu Hengrui Medicine Co., Ltd. | Bispecific antibody specifically bound to vegf and ang2 |
| EP4240832A4 (en) * | 2020-11-04 | 2025-01-01 | Fate Therapeutics, Inc. | Engineered ipsc and immune effector cells for heterogenous tumor control |
| CN116003591B (zh) * | 2022-12-12 | 2023-09-19 | 三门峡市眼科医院 | Ang-2抗体及其应用 |
Family Cites Families (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| USRE30985E (en) | 1978-01-01 | 1982-06-29 | Serum-free cell culture media | |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| US4485045A (en) | 1981-07-06 | 1984-11-27 | Research Corporation | Synthetic phosphatidyl cholines useful in forming liposomes |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
| US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
| US4544545A (en) | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
| US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
| GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
| US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| US5204244A (en) | 1987-10-27 | 1993-04-20 | Oncogen | Production of chimeric antibodies by homologous recombination |
| EP0435911B1 (en) | 1988-09-23 | 1996-03-13 | Cetus Oncology Corporation | Cell culture medium for enhanced cell growth, culture longevity and product expression |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
| US6797492B2 (en) | 1991-05-17 | 2004-09-28 | Merck & Co., Inc. | Method for reducing the immunogenicity of antibody variable domains |
| US5534615A (en) | 1994-04-25 | 1996-07-09 | Genentech, Inc. | Cardiac hypertrophy factor and uses therefor |
| US5869079A (en) | 1995-06-02 | 1999-02-09 | Oculex Pharmaceuticals, Inc. | Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents |
| US6884879B1 (en) | 1997-04-07 | 2005-04-26 | Genentech, Inc. | Anti-VEGF antibodies |
| ES2236634T3 (es) | 1997-04-07 | 2005-07-16 | Genentech, Inc. | Anticuerpos anti-vegf. |
| US7117096B2 (en) | 2001-04-17 | 2006-10-03 | Abmaxis, Inc. | Structure-based selection and affinity maturation of antibody library |
| GB0110029D0 (en) | 2001-04-24 | 2001-06-13 | Grosveld Frank | Transgenic animal |
| PL223153B1 (pl) | 2002-09-18 | 2016-10-31 | Allergan Inc | Urządzenie do wszczepiania implantu okulistycznego |
| GB0230203D0 (en) * | 2002-12-27 | 2003-02-05 | Domantis Ltd | Fc fusion |
| US7758859B2 (en) | 2003-08-01 | 2010-07-20 | Genentech, Inc. | Anti-VEGF antibodies |
| US20050282233A1 (en) | 2004-03-05 | 2005-12-22 | Ludwig Institute For Cancer Research | Multivalent antibody materials and methods for VEGF/PDGF family of growth factors |
| WO2006008548A2 (en) | 2004-07-22 | 2006-01-26 | Erasmus University Medical Centre Rotterdam | Binding molecules |
| US7691365B2 (en) * | 2004-09-28 | 2010-04-06 | Aprogen, Inc. | Methods of using chimeric coiled coil molecule to treat ischemic disease |
| HRP20110859T1 (hr) * | 2004-12-21 | 2011-12-31 | Medimmune Limited | Protutijela usmjerena na angiopoietin-2 i njihova upotreba |
| BRPI0706750A2 (pt) | 2006-01-25 | 2011-04-05 | Univ Erasmus Medical Ct | geração de anticorpos de cadeia pesada em animais transgênicos |
| TWI580694B (zh) | 2007-11-30 | 2017-05-01 | 建南德克公司 | 抗-ｖｅｇｆ抗體 |
| US8268314B2 (en) * | 2008-10-08 | 2012-09-18 | Hoffmann-La Roche Inc. | Bispecific anti-VEGF/anti-ANG-2 antibodies |
| CN102307902B (zh) * | 2008-12-10 | 2016-02-24 | 埃博灵克斯股份有限公司 | 用于治疗与血管发生相关的疾病和病症的针对血管生成素/Tie系统的氨基酸序列和包括其的多肽 |
| GB0905023D0 (en) * | 2009-03-24 | 2009-05-06 | Univ Erasmus Medical Ct | Binding molecules |
| TWI426920B (zh) * | 2010-03-26 | 2014-02-21 | Hoffmann La Roche | 雙專一性、雙價抗－ｖｅｇｆ／抗－ａｎｇ－２抗體 |
| US9527925B2 (en) * | 2011-04-01 | 2016-12-27 | Boehringer Ingelheim International Gmbh | Bispecific binding molecules binding to VEGF and ANG2 |
| CA2865464C (en) * | 2012-03-30 | 2022-07-12 | Boehringer Ingelheim International Gmbh | Ang2-binding molecules |
| RU2639287C2 (ru) * | 2012-06-27 | 2017-12-20 | Ф. Хоффманн-Ля Рош Аг | Способ отбора и получения высокоселективных и мультиспецифичных нацеливающих групп с заданными свойствами, включающих по меньшей мере две различные связывающие группировки, и их применения |
| SG11201408538PA (en) * | 2012-07-13 | 2015-02-27 | Roche Glycart Ag | Bispecific anti-vegf/anti-ang-2 antibodies and their use in the treatment of ocular vascular diseases |
| AU2013343099A1 (en) | 2012-11-09 | 2015-05-14 | Pfizer Inc. | Platelet-derived growth factor B specific antibodies and compositions and uses thereof |
| JO3405B1 (ar) | 2013-01-09 | 2019-10-20 | Regeneron Pharma | الأجسام المضادة لمضاد مستقبل عامل النمو المشتق من الصفائح الدموية - بيتا واستخداماتها |
| WO2014141192A1 (en) | 2013-03-15 | 2014-09-18 | Erasmus University Medical Center | Generation of heavy chain-only antibodies |
| US9902767B2 (en) * | 2013-07-29 | 2018-02-27 | Samsung Electronics Co., Ltd. | Method of blocking vascular leakage using an anti-ANG2 antibody |
| KR102146845B1 (ko) * | 2013-07-30 | 2020-08-21 | 삼성전자주식회사 | 앤지오포이에틴-2에 특이적으로 결합하는 항체 및 그의 용도 |
| AU2015345322A1 (en) * | 2014-11-10 | 2017-04-06 | F. Hoffmann-La Roche Ag | Anti-PDGF-B antibodies and methods of use |
| CN107849126B (zh) * | 2015-07-29 | 2022-04-08 | 阿勒根公司 | 仅有重链的抗ang-2抗体 |
| AU2016307943A1 (en) * | 2015-08-14 | 2018-02-15 | Allergan, Inc. | Heavy chain only antibodies to PDGF |
-
2016
- 2016-07-29 CN CN201680044324.2A patent/CN107849126B/zh not_active Expired - Fee Related
- 2016-07-29 WO PCT/US2016/044838 patent/WO2017020001A2/en not_active Ceased
- 2016-07-29 EP EP20187139.9A patent/EP3792279A3/en not_active Withdrawn
- 2016-07-29 RU RU2018103960A patent/RU2749674C2/ru active
- 2016-07-29 DK DK16748025.0T patent/DK3328886T3/da active
- 2016-07-29 JP JP2018504124A patent/JP6916776B2/ja not_active Expired - Fee Related
- 2016-07-29 CA CA2992660A patent/CA2992660A1/en active Pending
- 2016-07-29 US US15/223,855 patent/US10266589B2/en active Active
- 2016-07-29 ES ES16748025T patent/ES2828694T3/es active Active
- 2016-07-29 PL PL16748025T patent/PL3328886T3/pl unknown
- 2016-07-29 BR BR112018001762A patent/BR112018001762A2/pt not_active IP Right Cessation
- 2016-07-29 HU HUE16748025A patent/HUE051165T2/hu unknown
- 2016-07-29 EP EP16748025.0A patent/EP3328886B1/en active Active
- 2016-07-29 AU AU2016298398A patent/AU2016298398A1/en not_active Abandoned
-
2019
- 2019-04-16 US US16/385,384 patent/US11046756B2/en not_active Expired - Fee Related
-
2021
- 2021-06-28 US US17/361,180 patent/US20210324064A1/en not_active Abandoned
-
2022
- 2022-10-26 AU AU2022259761A patent/AU2022259761A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP3792279A3 (en) | 2021-07-07 |
| RU2018103960A (ru) | 2019-08-28 |
| DK3328886T3 (da) | 2020-11-02 |
| US20210324064A1 (en) | 2021-10-21 |
| PL3328886T3 (pl) | 2021-02-08 |
| RU2749674C2 (ru) | 2021-06-16 |
| US10266589B2 (en) | 2019-04-23 |
| US20170107279A1 (en) | 2017-04-20 |
| CN107849126B (zh) | 2022-04-08 |
| JP6916776B2 (ja) | 2021-08-11 |
| WO2017020001A2 (en) | 2017-02-02 |
| AU2022259761A1 (en) | 2022-12-01 |
| EP3792279A2 (en) | 2021-03-17 |
| AU2016298398A1 (en) | 2018-02-08 |
| EP3328886A2 (en) | 2018-06-06 |
| US11046756B2 (en) | 2021-06-29 |
| JP2018527327A (ja) | 2018-09-20 |
| RU2018103960A3 (enExample) | 2020-01-16 |
| BR112018001762A2 (pt) | 2018-09-18 |
| ES2828694T3 (es) | 2021-05-27 |
| EP3328886B1 (en) | 2020-09-16 |
| WO2017020001A3 (en) | 2017-03-16 |
| HK1253947A1 (en) | 2019-07-05 |
| US20190248882A1 (en) | 2019-08-15 |
| HUE051165T2 (hu) | 2021-03-01 |
| CN107849126A (zh) | 2018-03-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11046756B2 (en) | Heavy chain only antibodies to ANG-2 | |
| US20250333490A1 (en) | Heavy chain only antibodies to pdgf | |
| AU2024205262A1 (en) | Compositions and methods for treatment of diabetic macular edema | |
| KR102282134B1 (ko) | 인간 fcrn-결합 변형된 항체 및 사용 방법 | |
| TWI653243B (zh) | 遏止ＦｃＲｎ結合之抗ＩＧＦ－１Ｒ抗體及其治療血管性眼疾之用途 | |
| WO2018175319A1 (en) | Heavy chain only antibodies to vegf | |
| WO2022199603A1 (en) | Antibody fusion proteins and uses thereof | |
| TW202506728A (zh) | 活化素a受體樣1型(alk1)之雙特異性促效性抗體 | |
| US20220389120A1 (en) | Multispecific antagonists | |
| HK1253947B (en) | Heavy chain only antibodies to ang-2 | |
| TW202530256A (zh) | 多特異性抗原結合多肽之組合物及使用方法 | |
| WO2023083243A1 (zh) | 一种抗il-17/vegf双功能融合蛋白及其用途 | |
| KR20220069076A (ko) | 항-nrp1a 항체와 안구 또는 안구 질환 치료를 위한 이의 용도 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220131 |
|
| EEER | Examination request |
Effective date: 20220131 |
|
| EEER | Examination request |
Effective date: 20220131 |
|
| EEER | Examination request |
Effective date: 20220131 |