CN1703426A - 识别β-淀粉样肽的人源化抗体 - Google Patents
识别β-淀粉样肽的人源化抗体 Download PDFInfo
- Publication number
- CN1703426A CN1703426A CNA038058162A CN03805816A CN1703426A CN 1703426 A CN1703426 A CN 1703426A CN A038058162 A CNA038058162 A CN A038058162A CN 03805816 A CN03805816 A CN 03805816A CN 1703426 A CN1703426 A CN 1703426A
- Authority
- CN
- China
- Prior art keywords
- antibody
- residue
- seq
- immunoglobulin
- heavy chain
- 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.)
- Granted
Links
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 title description 8
- 238000000034 method Methods 0.000 claims abstract description 145
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 106
- 201000010099 disease Diseases 0.000 claims abstract description 100
- 238000011282 treatment Methods 0.000 claims abstract description 82
- 210000004556 brain Anatomy 0.000 claims abstract description 21
- 108060003951 Immunoglobulin Proteins 0.000 claims description 196
- 102000018358 immunoglobulin Human genes 0.000 claims description 196
- 150000001413 amino acids Chemical class 0.000 claims description 128
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 99
- 210000004027 cell Anatomy 0.000 claims description 58
- 230000027455 binding Effects 0.000 claims description 54
- 239000000427 antigen Substances 0.000 claims description 53
- 108091007433 antigens Proteins 0.000 claims description 53
- 102000036639 antigens Human genes 0.000 claims description 53
- 238000004458 analytical method Methods 0.000 claims description 44
- 239000012634 fragment Substances 0.000 claims description 43
- 238000006243 chemical reaction Methods 0.000 claims description 41
- 229920001184 polypeptide Polymers 0.000 claims description 39
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 36
- 230000009870 specific binding Effects 0.000 claims description 35
- 230000000295 complement effect Effects 0.000 claims description 34
- 102000005962 receptors Human genes 0.000 claims description 34
- 108020003175 receptors Proteins 0.000 claims description 34
- 239000012636 effector Substances 0.000 claims description 31
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims description 29
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 28
- 230000003941 amyloidogenesis Effects 0.000 claims description 27
- 206010002022 amyloidosis Diseases 0.000 claims description 26
- 238000000926 separation method Methods 0.000 claims description 24
- 102000039446 nucleic acids Human genes 0.000 claims description 23
- 108020004707 nucleic acids Proteins 0.000 claims description 23
- 150000007523 nucleic acids Chemical class 0.000 claims description 23
- 239000002773 nucleotide Substances 0.000 claims description 21
- 125000003729 nucleotide group Chemical group 0.000 claims description 21
- 239000003153 chemical reaction reagent Substances 0.000 claims description 20
- 230000002265 prevention Effects 0.000 claims description 20
- 230000001225 therapeutic effect Effects 0.000 claims description 19
- 125000000539 amino acid group Chemical group 0.000 claims description 18
- 238000004140 cleaning Methods 0.000 claims description 16
- 210000005036 nerve Anatomy 0.000 claims description 16
- 208000024891 symptom Diseases 0.000 claims description 15
- 241001465754 Metazoa Species 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 238000012544 monitoring process Methods 0.000 claims description 11
- 230000001404 mediated effect Effects 0.000 claims description 10
- 101000777550 Homo sapiens CCN family member 2 Proteins 0.000 claims description 9
- 208000010877 cognitive disease Diseases 0.000 claims description 9
- 102000047612 human CCN2 Human genes 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 8
- 208000028698 Cognitive impairment Diseases 0.000 claims description 7
- 230000037396 body weight Effects 0.000 claims description 7
- 201000010374 Down Syndrome Diseases 0.000 claims description 6
- 210000002966 serum Anatomy 0.000 claims description 6
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 5
- 230000013595 glycosylation Effects 0.000 claims description 5
- 238000006206 glycosylation reaction Methods 0.000 claims description 5
- 230000009261 transgenic effect Effects 0.000 claims description 5
- 230000008499 blood brain barrier function Effects 0.000 claims description 4
- 210000001218 blood-brain barrier Anatomy 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000011156 evaluation Methods 0.000 claims description 4
- 238000003384 imaging method Methods 0.000 claims description 4
- 238000001990 intravenous administration Methods 0.000 claims description 4
- 210000003928 nasal cavity Anatomy 0.000 claims description 4
- 238000007920 subcutaneous administration Methods 0.000 claims description 4
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 3
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 230000000926 neurological effect Effects 0.000 claims description 3
- 235000013336 milk Nutrition 0.000 claims description 2
- 239000008267 milk Substances 0.000 claims description 2
- 210000004080 milk Anatomy 0.000 claims description 2
- 230000004797 therapeutic response Effects 0.000 claims description 2
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 claims 2
- 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 claims 2
- 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 claims 2
- 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 claims 2
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 claims 2
- 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 claims 2
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims 2
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims 2
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims 2
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims 2
- 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 claims 2
- 102100022949 Immunoglobulin kappa variable 2-29 Human genes 0.000 claims 2
- 208000037259 Amyloid Plaque Diseases 0.000 abstract description 13
- 235000001014 amino acid Nutrition 0.000 description 102
- 229940024606 amino acid Drugs 0.000 description 101
- 241000699666 Mus <mouse, genus> Species 0.000 description 99
- 230000008859 change Effects 0.000 description 57
- 239000000370 acceptor Substances 0.000 description 46
- 239000003814 drug Substances 0.000 description 43
- 230000000694 effects Effects 0.000 description 34
- 239000000203 mixture Substances 0.000 description 32
- 230000036039 immunity Effects 0.000 description 28
- 108090000623 proteins and genes Proteins 0.000 description 28
- 230000035772 mutation Effects 0.000 description 25
- 238000012360 testing method Methods 0.000 description 25
- 230000006870 function Effects 0.000 description 21
- 108020004414 DNA Proteins 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- 102000006395 Globulins Human genes 0.000 description 14
- 108010044091 Globulins Proteins 0.000 description 14
- 238000003752 polymerase chain reaction Methods 0.000 description 13
- 108091033319 polynucleotide Proteins 0.000 description 13
- 102000040430 polynucleotide Human genes 0.000 description 13
- 239000002157 polynucleotide Substances 0.000 description 13
- 206010057249 Phagocytosis Diseases 0.000 description 12
- 230000008782 phagocytosis Effects 0.000 description 12
- 239000007790 solid phase Substances 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- 108091034117 Oligonucleotide Proteins 0.000 description 11
- 239000002671 adjuvant Substances 0.000 description 11
- 238000009826 distribution Methods 0.000 description 11
- 230000028993 immune response Effects 0.000 description 11
- 230000002163 immunogen Effects 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 230000002441 reversible effect Effects 0.000 description 11
- 108091035707 Consensus sequence Proteins 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 10
- 239000013604 expression vector Substances 0.000 description 10
- 210000000274 microglia Anatomy 0.000 description 10
- 238000005457 optimization Methods 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- 102000009490 IgG Receptors Human genes 0.000 description 9
- 108010073807 IgG Receptors Proteins 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 9
- 239000001963 growth medium Substances 0.000 description 9
- 230000035876 healing Effects 0.000 description 9
- 238000012216 screening Methods 0.000 description 9
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 8
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 8
- 238000004422 calculation algorithm Methods 0.000 description 8
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 8
- 238000001514 detection method Methods 0.000 description 8
- 210000004408 hybridoma Anatomy 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 238000012545 processing Methods 0.000 description 8
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 7
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 7
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 7
- 238000013461 design Methods 0.000 description 7
- 230000003053 immunization Effects 0.000 description 7
- 238000002649 immunization Methods 0.000 description 7
- 230000005847 immunogenicity Effects 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 230000007170 pathology Effects 0.000 description 7
- 210000001539 phagocyte Anatomy 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 241000196324 Embryophyta Species 0.000 description 6
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 6
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 6
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 6
- 108010076504 Protein Sorting Signals Proteins 0.000 description 6
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 6
- 235000004279 alanine Nutrition 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 108091036078 conserved sequence Proteins 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 238000003745 diagnosis Methods 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 229930182817 methionine Natural products 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 239000004474 valine Substances 0.000 description 6
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 5
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 230000000890 antigenic effect Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000009137 competitive binding Effects 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 235000013922 glutamic acid Nutrition 0.000 description 5
- 229960002989 glutamic acid Drugs 0.000 description 5
- 239000004220 glutamic acid Substances 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 5
- 102220335925 rs775094277 Human genes 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
- 102000009109 Fc receptors Human genes 0.000 description 4
- 108010087819 Fc receptors Proteins 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- 102220493683 HLA class II histocompatibility antigen, DRB1 beta chain_V67L_mutation Human genes 0.000 description 4
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 4
- 238000000137 annealing Methods 0.000 description 4
- 235000003704 aspartic acid Nutrition 0.000 description 4
- 238000011888 autopsy Methods 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 150000001576 beta-amino acids Chemical class 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000005336 cracking Methods 0.000 description 4
- 230000008021 deposition Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000004043 dyeing Methods 0.000 description 4
- 238000010353 genetic engineering Methods 0.000 description 4
- 238000009396 hybridization Methods 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 230000036737 immune function Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000011503 in vivo imaging Methods 0.000 description 4
- 229960000310 isoleucine Drugs 0.000 description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 102200087445 rs566961335 Human genes 0.000 description 4
- 102220188881 rs747642461 Human genes 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 238000012163 sequencing technique Methods 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 206010061818 Disease progression Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 102220582751 Glutathione S-transferase Mu 4_G27S_mutation Human genes 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 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
- 102220488187 Olfactory receptor 2A12_I29L_mutation Human genes 0.000 description 3
- 108010050254 Presenilins Proteins 0.000 description 3
- 238000012300 Sequence Analysis Methods 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 230000002860 competitive effect Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 230000005750 disease progression Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 210000005153 frontal cortex Anatomy 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000007917 intracranial administration Methods 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 230000035479 physiological effects, processes and functions Effects 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 229920000747 poly(lactic acid) Polymers 0.000 description 3
- 238000001742 protein purification Methods 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 102200082932 rs33929459 Human genes 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 101100230376 Acetivibrio thermocellus (strain ATCC 27405 / DSM 1237 / JCM 9322 / NBRC 103400 / NCIMB 10682 / NRRL B-4536 / VPI 7372) celI gene Proteins 0.000 description 2
- 206010069754 Acquired gene mutation Diseases 0.000 description 2
- 102100034112 Alkyldihydroxyacetonephosphate synthase, peroxisomal Human genes 0.000 description 2
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 2
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 102000000989 Complement System Proteins Human genes 0.000 description 2
- 108010069112 Complement System Proteins Proteins 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- 238000009007 Diagnostic Kit Methods 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 101000799143 Homo sapiens Alkyldihydroxyacetonephosphate synthase, peroxisomal Proteins 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- 241000446313 Lamella Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 102000015499 Presenilins Human genes 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 108091081021 Sense strand Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 101000980463 Treponema pallidum (strain Nichols) Chaperonin GroEL Proteins 0.000 description 2
- 238000005411 Van der Waals force Methods 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000006933 amyloid-beta aggregation Effects 0.000 description 2
- 238000000848 angular dependent Auger electron spectroscopy Methods 0.000 description 2
- 230000003302 anti-idiotype Effects 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 229960003121 arginine Drugs 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 230000006957 competitive inhibition Effects 0.000 description 2
- 238000005094 computer simulation Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000006059 cover glass Substances 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 238000009795 derivation Methods 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 239000003344 environmental pollutant Substances 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229960002885 histidine Drugs 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 230000008676 import Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 2
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 231100000719 pollutant Toxicity 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000037439 somatic mutation Effects 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 102100027831 14-3-3 protein theta Human genes 0.000 description 1
- 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 108010022579 ATP dependent 26S protease Proteins 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 102000001049 Amyloid Human genes 0.000 description 1
- 108010094108 Amyloid Proteins 0.000 description 1
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 1
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 1
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 108010060159 Apolipoprotein E4 Proteins 0.000 description 1
- 241000700663 Avipoxvirus Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108091033380 Coding strand Proteins 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 108091092584 GDNA Proteins 0.000 description 1
- 241001200922 Gagata Species 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
- 101710182312 High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010065042 Immune reconstitution inflammatory syndrome Diseases 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000008192 Lactoglobulins Human genes 0.000 description 1
- 108010060630 Lactoglobulins Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 240000002769 Morchella esculenta Species 0.000 description 1
- 235000002779 Morchella esculenta Nutrition 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101000746372 Mus musculus Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
- 101001082628 Mus musculus H-2 class II histocompatibility antigen gamma chain Proteins 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001482592 Oreamnos americanus Species 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 241000700625 Poxviridae Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000710961 Semliki Forest virus Species 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 241000710960 Sindbis virus Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 101150117115 V gene Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 208000000260 Warts Diseases 0.000 description 1
- GLLRIXZGBQOFLM-UHFFFAOYSA-N Xanthorin Natural products C1=C(C)C=C2C(=O)C3=C(O)C(OC)=CC(O)=C3C(=O)C2=C1O GLLRIXZGBQOFLM-UHFFFAOYSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 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 1
- 229960005305 adenosine Drugs 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 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
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000003429 anti-cardiolipin effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 101150031224 app gene Proteins 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 150000001510 aspartic acids Chemical class 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 239000003855 balanced salt solution Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000003150 biochemical marker Substances 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000005013 brain tissue 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
- 125000001314 canonical amino-acid group Chemical group 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 102000006834 complement receptors Human genes 0.000 description 1
- 108010047295 complement receptors Proteins 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 230000000536 complexating effect Effects 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
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000008473 connective tissue growth Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000003181 encephalopathic effect Effects 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 238000009432 framing Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- XUWPJKDMEZSVTP-LTYMHZPRSA-N kalafungina Chemical compound O=C1C2=C(O)C=CC=C2C(=O)C2=C1[C@@H](C)O[C@H]1[C@@H]2OC(=O)C1 XUWPJKDMEZSVTP-LTYMHZPRSA-N 0.000 description 1
- 206010023497 kuru Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 238000003754 machining Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 108700039855 mouse a Proteins 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 230000001662 opsonic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 208000008494 pericarditis Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical class CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 102220093344 rs749571694 Human genes 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000013391 scatchard analysis Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- -1 shitosan Chemical class 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 201000010153 skin papilloma Diseases 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- OFVLGDICTFRJMM-WESIUVDSSA-N tetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O OFVLGDICTFRJMM-WESIUVDSSA-N 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000011820 transgenic animal model Methods 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 150000003626 triacylglycerols Chemical class 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
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000003934 vacuole Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000004804 winding Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—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
- C07K2317/50—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
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Abstract
Description
链 | VL | VH |
小鼠的亚型 | II | Ib |
人的亚型 | II | II |
稀有氨基酸(概率百分数) | K107(0.542%) | T3,I11,L12,F24,S41,N75,D83,A85 |
按照Chothia典型的类型 | L1:类4[1rmf]L2:类1[1lmk]L3:类1[1tet] | H1:类3[1ggi]H2:类1 |
最接近的小鼠MAb解析结构 | 2PCP(2.2) | 1ETZ(2.6) |
与模型模板的同源性 | 94% | 80% |
人的框架序列 | KABID 005036 | 1-KABID 0003332-AAB35009/1F73-AAD53816 |
人框架的种系对照 | A3/x12690&A19/X63397 | 1:VH4-39/AB019439/BAA75036.12:VH2-5/AB019440/BAA75057.1 |
抗体12B4人源化12B4v1人源化12B4v2人源化12B4v3种系A19Kabat ID005036Kabat ID000333种系VH4-61种系VH4-39 | VL核苷酸 序列SEQ IDNO:1SEQ IDNO:5SEQ IDNO:1SEQ IDNO:1SEQ IDNO:29SEQ IDNO:31 | VL氨基酸 序列SEQ IDNO:2SEQ IDNO:6SEQ IDNO:2SEQ IDNO:2SEQ IDNO:30SEQ IDNO:32 | VH核苷酸 序列SEQ IDNO:3SEQ IDNO:7SEQ IDNO:9SEQ IDNO:11SEQ IDNO:33SEQ IDNO:35SEQ IDNO:37 | VH氨基酸 序列SEQ IDNO:4SEQ IDNO:8SEQ IDNO:10SEQ IDNO:12SEQ IDNO:34SEQ IDNO:36SEQ IDNO:38 | ||
PBS | TY 11/15 | 12B4 | 3D6,10mg/kg | 3D6,1mg/kg | 3D6,10mg/kg/4周 | 活性 | |
N | 31 | 30 | 33 | 29 | 31 | 32 | 24 |
中值(%AB) | 15.182297 | 13.303288 | 2.317222 | 0.865671 | 2.286513 | 1.470956 | 2.162772 |
范围 | 0.160-31.961 | 0-61.706 | 0-14.642 | 0-7.064 | 0.077-63.362 | 0-10.688 | 0-30.715 |
p值(*M-W) | .9425ns | ***<.0001 | ***.0001 | ***<.0001 | ***<.0001 | ***.0004 | |
变化% | N/A | 12% | 85% | 94% | 85% | 90% | 86% |
PBS | TY 11/15 | 12B4 | 3D6,10mg/kg | 3D6,1mg/kg | 3D6,10mg/kg/4周 | 活性 | |
N | 31 | 30 | 33 | 29 | 31 | 32 | 24 |
中值(%AB) | 0.3946 | 0.3958 | 0.0816 | 0.4681 | 0.3649 | 0.4228 | 0.2344 |
范围 | 0-1.3828 | 0-2.6800 | 0-0.8127 | 0-1.3098 | 0-1.5760 | 0-1.8215 | 0-1.1942 |
p值(*M-W) | .8967ns | ***.0002 | .9587ns | .6986ns | >.9999 | ***.0381 | |
变化% | 0% | 79% | 0% | 7% | 0% | 41% |
变化 | VL(111个残基) | VH(123个残基) |
人→鼠:框架 | 1/111 | 9/123 |
CDR1 | 8/16 | 7/7 |
CDR2 | 3/7 | 8/16 |
CDR3 | 6/8 | 10/13 |
人→鼠总数 | 18/111(16%) | 34/123(28%,第二版23%) |
鼠→人:框架 | 10/111 | 16/123 |
回复突变说明 | 1、I12V:典型位置 | 2、典型:V24F、G27F、I29L和V71K3、包装:无4、微调:L2V*、I48L*#、G49A*、V67L*和F78V*# |
受体说明 | 5、KABID 005036/GenBankAcc#-X679046、CDRs来自与供体小鼠相同的典型结构组;7、来自SLE病人的抗心磷脂/ss DNA自身抗体 | 8、KABID 000333/GenBankAcc#-X544379、CDRs来自与供体小鼠相同的典型结构组;10、来自RA病人的类风湿因子mAb |
KAB# | # | 类型 | 小鼠12B4 VL | 人12B4 VL | KABID005036 | A19-株系 | 注释 |
12345678910111213141516171819202122232425262727A27B27C27D27E | 1234567891011121314151617181920212223242526272829303132 | FR1CDR1 | DVLMTQTPLSLPVSLGDQASISCRSSQNIVHS | DVVMTQSPLSLPVTPGEPASISCRSSQNIVHS | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHR | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHS | 典型的——在第1、2、3版中回复突变 |
28293031323334353637383940414243444546474849505152535455565758596061626364 | 33343536373839404142434445464748495051525354555657585960616263646566676869 | FR2CDR2FR3 | NGNTYLEWYLQKPGQSPKLLIYKVSNRFSGVPDRFSG | NGNTYLEWYLQKPGQSPQLLIYKVSNRFSGVPDRFSG | YGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSG | NGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSG |
6566676869707172737475767778798081828384858687888990919293949596979899100101 | 707172737475767778798081828384858687888990919293949596979899100101102103104105106 | CDR3FR4 | SGSGTDFTLKISRVEAEDLGVYYCFQGSHVPLTFGAG | SGSGTDFTLKISRVEAEDVGVYYCFQGSHVPLTFGQG | SGSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQG | SGSGTDFTLKISRVEAEDVGVYYCMQALQTP |
102103104105106106A | 107108109110111112 | TKLELK | TKLEIK | TKLEIK |
KAB# | # | 类型 | 小鼠12B4VH | 人12B4VHv1 | KABID000333 | VH4-39种系 | VH4-61种系 | 注释 |
1234567891011121314151617181920212223 | 1234567891011121314151617181920212223 | FR1 | QVTLKESGPGILQPSQTLSLTCS | QVQLQESGPGLVKPSETLSLTCT | QLQLQESGPGLVKPSETLSLTCT | QLQLQESGPGLVKPSETLSLTCT | QVQLQESGPGLVKPSETLSLTCT | 微调的——只在第1版中回复突变 |
242526 | 242526 | FSG | FSG | VSG | VSG | 典型的——在V 第1、2、3版中回复突变SG典型的——在 | |
2728 | 2728 | FS | FS | GS | GS | G 第1、2、3版中回复突变S | |
29 | 29 | L | L | I | I | 典型的——在V 第1、2、3版中回复突变 | |
30313233343535A35B363738394041424344454647 | 3031323334353637383940414243444546474849 | CDR1FR2 | STNGMGVSWIRQPSGKGLEW | STNGMGVSWIRQPPGKGLEW | SRGSHYWGWIRQPPGKGLEW | SSSSYYWGWIRQPPGKGLEW | SSGGYYWSWIRQPPGKGLEW |
4859 | 5051 | LA | LA | IG | IG | 微调的——只I 在第1、3版中回复突变微调的——只在第1版中回 |
5051525354555657585960616263646566 | 5253545556575859606162636465666768 | CDR2FR3 | HIYWDEDKRYNPSLKSR | HIYWDEDKRYNPSLKSR | SIYYSGNTYFNPSLKSR | SIYYSGSTYYNPSLKSR | YIYYSGSTNYNPSLKSR | 复突变 |
67 | 69 | L | L | V | V | V | 微调的——只在第1版中回复突变 | |
686970 | 707172 | TIS | TIS | TIS | TIS | TIS | ||
71 | 73 | K | K | V | V | V | 典型的——在第1、2、3版中回复突变 | |
727374757677 | 747576777879 | DTSNNQ | DTSKNQ | DTSKNQ | DTSKNQ | DTSKNQ | ||
7879 | 8081 | VF | VS | FS | FS | FS | 微调的——在第1、3版中回复突变 |
80818282A82B82C8384858687888990919293949595A96979899100100A100B100C100D100E101102103104105106107 | 82838485868788899091929394959696979899100101102103104105106107108109110111112113114115116117 | CDR3FR4 | LKITNVDTADTATYYCARR-RIIYDVEDYFDYWGQGT | LKLSSVTAADTAVYYCARR-RIIYDVEDYFDYWGQGT | LKLSSVTAADTAVYYCARLGPDDYTLDG-MDVWGQGT | LKLSSVTAADTAVYYCAR | LKLSSVTAADTAVYYCAR |
108109110111112113 | 118119120121122123 | TLTVSS | TVTVSS | TVTVSS |
DNA# | 大小 | 是否编码链? | 序列 | 注释 |
4881 | 135 | 是 | gagattaagcttgccgccaccATGAGGCTCCCTGCTCAGCTCCTGGGGCTGCTAATGCTCTGGGTCTCTGGATCCAGTGGGGATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCG | 通过Oligos等合成人12B4 VLv1A引物。nts 1>11512B4 VLv1.保守的有义链。加上HindIII位点+Kozak共有序列。 |
SEQ ID NO:13 | ||||
4882 | 131 | 否 | AGGAGCTGTGGAGACTGCCCTGGCTTCTGCAGGTACCATTCCAAATAGGTGTTTCCATTACTATGAACAATGTTCTGACTAGACCTGCAGGAGATGGAGGCCGGCTCTCCAGGGGTGACGGGCAGGGAGAG | 通过Oligos等合成人12B4 VLv1B引物。反向互补DNA序列12B4 VLv1保守序列(85,215)。 |
SEQ ID NO:14 | ||||
4883 | 132 | 是 | TGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTACAAAGTTTCCAACCGATTTTCTGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAGTGGAGGCTG | 通过Oligos等合成人12B4 VLv1C引物。nts 185>31612B4 VLv1.保守的有义链。 |
SEQ ID NO:15 | ||||
4884 | 130 | 否 | tgatatggatccactcacGTTTGATCTCCAGCTTGGTCCCCTGACCGAACGTGAGCGGAACATGTGAACCTTGAAAGCAGTAATAAACCCCAACATCCTCAGCCTCCACTCTGCTGATTTTCAGTGTAAA | 通过Oligos等合成人12B4 VLv1D引物。反向互补DNA序列12B4 VLv1保守序列(286,397)。加上拼接的供体+BamHI位点。 |
SEQ ID NO:16 | ||||
4885 | 143 | 是 | gagataaagcttgccgccaccATGAAGCACCTGTGGTTCTTCCTCCTGCTGGTGGCAGCTCCCAGATGGGTCCTGTCCCAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTG | 通过Oligos等合成人12B4 VHv1A引物。12B4VHv1.保守序列nts 1-122。加上Kozak共有序列和HindIII位点。 |
SEQ ID NO:17 | ||||
4886 | 137 | 否 | TCCTCATCCCAATAGATGTGTGCCAGCCACTCCAGTCCCTTCCCTGGGGGCTGCCGGATCCAGCTCACACCCATACCATTAGTGCTCAGGGAAAAACCAGAGAAAGTGCAGGTGAGGGACAGGGTCTCCGAAGGCTT | 通过Oligos等合成人12B4 VHv1B引物。反向互补DNA序列12B4 VHv1保守序列(94,230)。 |
SEQ ID NO:18 | ||||
4887 | 138 | 是 | GTGGCTGGCACACATCTATTGGGATGAGGACAAGCGCTATAACCCATCCCTCAAGAGTCGACTCACCATATCAAAGGACACGTCCAAGAACCAGGTATCCCTGAAGCTGAGCTCTGTGACCGCTGCAGACACGGCCGT | 通过Oligos等合成人12B4 VHv1C引物。12B4 VHv1.保守序列nts 201-338。 |
SEQ ID NO:19 | ||||
4888 | 139 | 否 | tcatatggatccactcacCTGAGGAGACGGTGACCGTGGTCCCTTGGCCCCAGTAGTCAAAGTAGTCCTCAACATCATAGATGATCCTCCTTCTCGCACAGTAATACACGGCCGTGTCTGCAGCGGTCACAGAGCTCAG | 通过Oligos等合成人12B4 VHv1D引物。反向互补DNA序列12B4 VHv1保守序列(307,427)。在3’端加上拼接的供体+BamHI位点。 |
SEQ ID NO:20 | ||||
4889 | 22 | 是 | gag att aag ctt gcc gcc acc A | 人12B4 VLv1,A+B正向引物%A+T=45.45[10];%C+G=54.55[12];Davis,Botstein,Roth熔点温度64.54℃ |
SEQ ID NO:21 | ||||
4890 | 21 | 否 | AGG AGC TGT GGA GAC TGC CCT | 人12B4VLv1,A+B反向引物%A+T=38.10[8];%C+G=61.90[13];Davis,Botstein,Roth熔点温度66.47℃ |
SEQ ID NO:22 |
4891 | 20 | 是 | TGC AGA AGC CAG GGC AGT CT | 人12B4 VLv1,C+D正向引物%A+T=40.00[8];%C+G=60.00[12];Davis,Botstein,Roth熔点温度64.50℃ |
SEQ ID NO:23 | ||||
4892 | 28 | 否 | tga tat gga tcc act cac GTT TGA TCT C | 人12B4 VLv1,C+D反向引物%A+T=57.14[16];%C+G=42.86[12];Davis,Botstein,Roth熔点温度64.61℃ |
SEQ ID NO:24 | ||||
4893 | 23 | 是 | gag ata aagcttgccgcc acc AT | 人12B4 VHv1,A+B正向引物%A+T=47.83[11];%C+G=52.17[12];Davis,Botstein,Roth熔点温度64.55℃ |
SEQ ID NO:25 | ||||
4894 | 24 | 否 | TCC TCA TCC CAA TAG ATG TGT GCC | 人12B4 VHv1,A+B反向引物%A+T=50.00[12];%C+G=50.00[12];Davis,Botstein,Roth熔点温度64.57℃ |
SEQ ID NO:26 | ||||
4895 | 22 | 是 | GTG GCT GGC ACA CAT CTA TTG G | 人12B4 VHv1,C+D正向引物%A+T=45.45[10];%C+G=54.55[12];Davis,Botstein,Roth熔点温度64.54℃ |
SEQ ID NO:27 | ||||
4896 | 24 | 否 | tca tat gga tcc act cac CTG AGG | 人12B4 VHv1,C+D正向引物%A+T=50.00[12];%C+G=50.00[12];Davis,Botstein,Roth熔点温度64.57℃ |
SEQ ID NO:28 |
Claims (115)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US36375102P | 2002-03-12 | 2002-03-12 | |
US60/363,751 | 2002-03-12 | ||
PCT/US2003/007715 WO2003077858A2 (en) | 2002-03-12 | 2003-03-12 | Humanized antibodies that recognize beta amyloid peptide |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1703426A true CN1703426A (zh) | 2005-11-30 |
CN1703426B CN1703426B (zh) | 2010-04-28 |
Family
ID=28041806
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN038058162A Expired - Fee Related CN1703426B (zh) | 2002-03-12 | 2003-03-12 | 识别β-淀粉样肽的人源化抗体 |
Country Status (30)
Country | Link |
---|---|
US (2) | US7256273B2 (zh) |
EP (1) | EP1554311B1 (zh) |
JP (1) | JP2006503549A (zh) |
KR (2) | KR20110027846A (zh) |
CN (1) | CN1703426B (zh) |
AR (1) | AR038953A1 (zh) |
AU (1) | AU2003214152B2 (zh) |
BR (1) | BR0308143A (zh) |
CA (1) | CA2478049C (zh) |
CO (1) | CO5611164A2 (zh) |
EA (1) | EA010902B1 (zh) |
EC (1) | ECSP045314A (zh) |
ES (1) | ES2389541T3 (zh) |
GE (1) | GEP20084474B (zh) |
HK (1) | HK1085222A1 (zh) |
HR (1) | HRP20040950A2 (zh) |
IL (2) | IL163626A0 (zh) |
IS (1) | IS7499A (zh) |
MX (1) | MXPA04008740A (zh) |
MY (1) | MY139983A (zh) |
NO (1) | NO20043992L (zh) |
NZ (1) | NZ535769A (zh) |
PE (1) | PE20040207A1 (zh) |
PL (1) | PL215258B1 (zh) |
SG (1) | SG180018A1 (zh) |
TW (1) | TWI328116B (zh) |
UA (1) | UA89469C2 (zh) |
UY (1) | UY27721A1 (zh) |
WO (1) | WO2003077858A2 (zh) |
ZA (1) | ZA200406616B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105348387A (zh) * | 2010-08-14 | 2016-02-24 | Abbvie公司 | β淀粉样蛋白结合蛋白 |
Families Citing this family (124)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI239847B (en) | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
US7179892B2 (en) * | 2000-12-06 | 2007-02-20 | Neuralab Limited | Humanized antibodies that recognize beta amyloid peptide |
US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
US20080050367A1 (en) * | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
US7790856B2 (en) | 1998-04-07 | 2010-09-07 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize beta amyloid peptide |
US6787523B1 (en) * | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
US7700751B2 (en) | 2000-12-06 | 2010-04-20 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize β-amyloid peptide |
TWI255272B (en) * | 2000-12-06 | 2006-05-21 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
US7521053B2 (en) * | 2001-10-11 | 2009-04-21 | Amgen Inc. | Angiopoietin-2 specific binding agents |
US7658924B2 (en) * | 2001-10-11 | 2010-02-09 | Amgen Inc. | Angiopoietin-2 specific binding agents |
AR038568A1 (es) * | 2002-02-20 | 2005-01-19 | Hoffmann La Roche | Anticuerpos anti-a beta y su uso |
MY139983A (en) | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
KR20050118669A (ko) * | 2003-02-01 | 2005-12-19 | 뉴랄랩 리미티드 | 가용성 a-베타에 대한 항체를 생성하기 위한 능동 면역화 |
TWI306458B (en) * | 2003-05-30 | 2009-02-21 | Elan Pharma Int Ltd | Humanized antibodies that recognize beta amyloid peptide |
JP5068072B2 (ja) * | 2003-06-27 | 2012-11-07 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | 連結ペプチドを含む改変された結合分子 |
US20060024667A1 (en) * | 2004-07-29 | 2006-02-02 | Karen Manucharyan | Compositions and methods for Alzheimer's disease |
EA016357B1 (ru) * | 2004-07-30 | 2012-04-30 | Ринат Ньюросайенс Корп. | Антитела, направленные против бета-амилоидного пептида, и способы их применения |
US7300773B2 (en) | 2004-08-27 | 2007-11-27 | Wyeth Research Ireland Limited | Production of TNFR-Ig |
TWI374935B (en) * | 2004-08-27 | 2012-10-21 | Pfizer Ireland Pharmaceuticals | Production of α-abeta |
US7294484B2 (en) * | 2004-08-27 | 2007-11-13 | Wyeth Research Ireland Limited | Production of polypeptides |
WO2006042158A2 (en) * | 2004-10-05 | 2006-04-20 | Wyeth | Methods and compositions for improving recombinant protein production |
WO2006066089A1 (en) * | 2004-12-15 | 2006-06-22 | Neuralab Limited | Humanized amyloid beta antibodies for use in improving cognition |
AR051800A1 (es) * | 2004-12-15 | 2007-02-07 | Wyeth Corp | Anticuerpos a beta usados en mejorar la cognicion |
TW200636066A (en) * | 2004-12-15 | 2006-10-16 | Elan Pharm Inc | Humanized antibodies that recognize beta amyloid peptide |
KR20070100346A (ko) * | 2005-01-05 | 2007-10-10 | 바이오겐 아이덱 엠에이 인코포레이티드 | 크립토 결합 분자 |
AU2006208226A1 (en) * | 2005-01-24 | 2006-08-03 | Amgen Inc. | Humanized anti-amyloid antibody |
KR20070107079A (ko) * | 2005-01-28 | 2007-11-06 | 와이어쓰 | 안정화된 액체 폴리펩타이드 제형 |
GT200600031A (es) * | 2005-01-28 | 2006-08-29 | Formulacion anticuerpo anti a beta | |
MY148086A (en) * | 2005-04-29 | 2013-02-28 | Rinat Neuroscience Corp | Antibodies directed against amyloid-beta peptide and methods using same |
EP2388274A1 (en) | 2005-06-17 | 2011-11-23 | Janssen Alzheimer Immunotherapy | Methods of purifying anti A Beta antibodies |
EP1954718B1 (en) | 2005-11-30 | 2014-09-03 | AbbVie Inc. | Anti-a globulomer antibodies, antigen-binding moieties thereof, corresponding hybridomas, nucleic acids, vectors, host cells, methods of producing said antibodies, compositions comprising said antibodies, uses of said antibodies and methods of using said antibodies |
PT1976877E (pt) | 2005-11-30 | 2014-04-29 | Abbvie Inc | Anticorpos monoclonais contra proteína beta-amilóide e suas utilizações |
CA2632822C (en) | 2005-12-12 | 2018-08-28 | Ruth Greferath | A beta 1-42 specific monoclonal antibodies with therapeutic properties |
UA99097C2 (ru) * | 2005-12-12 | 2012-07-25 | Ф. Хоффманн-Ля Рош Аг | Композиция, содержащая антитела к амилоиду бета 4, имеющие гликозилированный вариабельный участок |
US8784810B2 (en) | 2006-04-18 | 2014-07-22 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases |
WO2008011348A2 (en) | 2006-07-14 | 2008-01-24 | Ac Immune S.A. | Humanized antibody against amyloid beta |
US7744890B2 (en) | 2006-10-12 | 2010-06-29 | Wyeth Llc | Methods and compositions with reduced opalescence |
WO2008070284A2 (en) | 2006-10-16 | 2008-06-12 | Johnnie B. Byrd, Sr. Alzheimer's Center And Research Institute | Amyloid beta peptides and methods of uses thereof |
US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
EA017611B1 (ru) * | 2007-01-05 | 2013-01-30 | Юнивэсэти Оф Цюрих | Способ получения связывающей молекулы, специфичной к белку, ассоциированному с расстройством, или антитела или его связывающего фрагмента или по меньшей мере одной цепи иммуноглобулина, связывающих вышеуказанный белок (варианты), связывающая молекула, антитело, цепь иммуноглобулина или их связывающий фрагмент (варианты), антиген, полинуклеотид, вектор и клетка-хозяин, их включающие композиция и набор и способ диагностики или лечения неврологических расстройств посредством |
IL199534A (en) | 2007-01-05 | 2013-01-31 | Univ Zuerich | An isolated human antibody capable of detecting a neoepitope in a disease-related protein, a polynucleotide encoding an antibody, a vector containing the polynucleotide, a host cell containing the polynucleotide or vector, a preparation containing the antibody and related methods and uses. |
WO2008084402A2 (en) | 2007-01-11 | 2008-07-17 | Philipps-Universitaet Marburg | Diagnosis and treatment of alzheimer's and other neurodementing diseases |
US20100311767A1 (en) | 2007-02-27 | 2010-12-09 | Abbott Gmbh & Co. Kg | Method for the treatment of amyloidoses |
JP5930573B2 (ja) | 2007-03-01 | 2016-06-15 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤の新規使用 |
DK2142514T3 (da) | 2007-04-18 | 2015-03-23 | Probiodrug Ag | Thioureaderivater som glutaminylcyclase-inhibitorer |
KR20100016661A (ko) * | 2007-04-18 | 2010-02-12 | 얀센 알츠하이머 이뮤노테라피 | 대뇌 아밀로이드 혈관병증의 예방 및 치료 |
US8003097B2 (en) | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
US8613923B2 (en) | 2007-06-12 | 2013-12-24 | Ac Immune S.A. | Monoclonal antibody |
US8048420B2 (en) | 2007-06-12 | 2011-11-01 | Ac Immune S.A. | Monoclonal antibody |
EP2182983B1 (en) * | 2007-07-27 | 2014-05-21 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases with humanised anti-abeta antibodies |
WO2009048539A2 (en) | 2007-10-05 | 2009-04-16 | Genentech, Inc. | Monoclonal antibody |
JO3076B1 (ar) | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | نظم العلاج المناعي المعتمد على حالة apoe |
CA2707309A1 (en) | 2007-12-18 | 2009-06-25 | Acumen Pharmaceuticals, Inc. | Novel addl receptor polypeptides, polynucleotides and host cells for recombinant production |
WO2009085200A2 (en) | 2007-12-21 | 2009-07-09 | Amgen Inc. | Anti-amyloid antibodies and uses thereof |
PT2237803E (pt) * | 2007-12-28 | 2015-10-16 | Prothena Biosciences Ltd | Tratamento e profilaxia da amiloidose |
AU2009211635B2 (en) | 2008-02-08 | 2014-06-26 | Immunas Pharma, Inc. | Antibody capable of binding specifically to Abeta-oligomer, and use thereof |
JO2913B1 (en) | 2008-02-20 | 2015-09-15 | امجين إنك, | Antibodies directed towards angiopoietin-1 and angiopoietin-2 proteins and their uses |
JP2011521009A (ja) | 2008-05-23 | 2011-07-21 | シワ コーポレイション | 再生を促進させる方法、組成物及び装置 |
US9085614B2 (en) | 2008-08-01 | 2015-07-21 | Immunas Pharma, Inc. | Antibodies that specifically bind to Aβ oligomers and uses thereof |
US9067981B1 (en) | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
EP3521309A1 (en) | 2008-12-19 | 2019-08-07 | Biogen International Neuroscience GmbH | Human anti-alpha-synuclein antibodies |
US8614297B2 (en) | 2008-12-22 | 2013-12-24 | Hoffmann-La Roche Inc. | Anti-idiotype antibody against an antibody against the amyloid β peptide |
DK2419447T3 (en) | 2009-04-17 | 2017-09-25 | Immunas Pharma Inc | ANTIBODIES THAT SPECIFICALLY BIND TO A BETA OLIGOMER AND USE THEREOF |
ES2624835T3 (es) | 2009-08-06 | 2017-07-17 | Immunas Pharma, Inc. | Anticuerpos que se unen específicamente a los oligómeros A beta y uso de los mismos |
CA2772488C (en) | 2009-09-11 | 2018-04-17 | Probiodrug Ag | Heterocyclic derivatives as inhibitors of glutaminyl cyclase |
WO2011075185A1 (en) | 2009-12-18 | 2011-06-23 | Oligasis | Targeted drug phosphorylcholine polymer conjugates |
EP2542581A4 (en) | 2010-03-01 | 2014-01-22 | David Gladstone Inst | SPECIFIC APOLIPOPROTEIN ANTIBODY AND METHODS OF USING SAME |
JP6026284B2 (ja) | 2010-03-03 | 2016-11-16 | プロビオドルグ エージー | グルタミニルシクラーゼの阻害剤 |
BR112012022102A2 (pt) | 2010-03-03 | 2017-01-10 | Boehringer Ingelheim Int | polipeptídeos de ligação a a-beta. |
US8269019B2 (en) | 2010-03-10 | 2012-09-18 | Probiodrug Ag | Inhibitors |
JP2013523182A (ja) | 2010-04-15 | 2013-06-17 | アボット・ラボラトリーズ | アミロイドベータ結合タンパク質 |
EP2560953B1 (en) | 2010-04-21 | 2016-01-06 | Probiodrug AG | Inhibitors of glutaminyl cyclase |
CA2803937A1 (en) * | 2010-06-30 | 2012-01-05 | Mount Sinai Hospital | Reagents and methods for diagnosing conditions associated with hydroxylated hif 1-a |
RU2607368C2 (ru) | 2010-07-30 | 2017-01-10 | Ац Иммуне С.А. | Безопасные и функциональные гуманизированные антитела |
US9649376B2 (en) | 2010-09-27 | 2017-05-16 | Siwa Corporation | Selective removal of age-modified cells for treatment of atherosclerosis |
US8721571B2 (en) | 2010-11-22 | 2014-05-13 | Siwa Corporation | Selective removal of cells having accumulated agents |
US8530670B2 (en) | 2011-03-16 | 2013-09-10 | Probiodrug Ag | Inhibitors |
TR201815563T4 (tr) | 2011-06-23 | 2018-11-21 | Biogen Int Neuroscience Gmbh | Anti-alfa sinüklein bağlayıcı moleküller. |
JP2012034697A (ja) * | 2011-09-16 | 2012-02-23 | Janssen Alzheimer Immunotherapy | βアミロイドペプチドを認識するヒト化抗体 |
RU2015105588A (ru) | 2012-07-19 | 2016-09-10 | Редвуд Байосайнс, Инк. | Антитело, специфическое к cd22, и способы его применения |
EP2999716A2 (en) | 2013-05-20 | 2016-03-30 | F. Hoffmann-La Roche AG | Anti-transferrin receptor antibodies and methods of use |
JP2014001232A (ja) * | 2013-09-02 | 2014-01-09 | Janssen Alzheimer Immunotherapy | アミロイド原性疾患の処置 |
EP3041513B1 (en) | 2013-09-08 | 2020-08-05 | Kodiak Sciences Inc. | Factor viii zwitterionic polymer conjugates |
US9840553B2 (en) | 2014-06-28 | 2017-12-12 | Kodiak Sciences Inc. | Dual PDGF/VEGF antagonists |
IL251210B2 (en) | 2014-09-19 | 2023-12-01 | Siwa Corp | Anti-aging antibodies for the treatment of inflammation and autoimmune disorders |
WO2016061562A2 (en) | 2014-10-17 | 2016-04-21 | Kodiak Sciences Inc. | Butyrylcholinesterase zwitterionic polymer conjugates |
US11008403B2 (en) | 2014-11-19 | 2021-05-18 | Genentech, Inc. | Anti-transferrin receptor / anti-BACE1 multispecific antibodies and methods of use |
US10508151B2 (en) | 2014-11-19 | 2019-12-17 | Genentech, Inc. | Anti-transferrin receptor antibodies and methods of use |
MA41115A (fr) | 2014-12-02 | 2017-10-10 | Biogen Int Neuroscience Gmbh | Procédé de traitement de la maladie d'alzheimer |
WO2016094566A2 (en) | 2014-12-10 | 2016-06-16 | Genentech, Inc. | Blood brain barrier receptor antibodies and methods of use |
US10358502B2 (en) | 2014-12-18 | 2019-07-23 | Siwa Corporation | Product and method for treating sarcopenia |
US9993535B2 (en) | 2014-12-18 | 2018-06-12 | Siwa Corporation | Method and composition for treating sarcopenia |
LT3313879T (lt) | 2015-06-24 | 2022-03-25 | F. Hoffmann-La Roche Ag | Antikūnai prieš transferino receptorių su pritaikytu giminingumu |
NZ741067A (en) | 2015-10-02 | 2023-07-28 | Hoffmann La Roche | Bispecific anti-human cd20/human transferrin receptor antibodies and methods of use |
AR106189A1 (es) | 2015-10-02 | 2017-12-20 | Hoffmann La Roche | ANTICUERPOS BIESPECÍFICOS CONTRA EL A-b HUMANO Y EL RECEPTOR DE TRANSFERRINA HUMANO Y MÉTODOS DE USO |
CN108350052A (zh) * | 2015-11-09 | 2018-07-31 | 英属哥伦比亚大学 | 淀粉样蛋白β中间区域中的表位及其构象选择性抗体 |
CA3004498A1 (en) * | 2015-11-09 | 2017-05-18 | Neil R. Cashman | Amyloid beta epitopes and antibodies thereto |
CA3004482A1 (en) | 2015-11-09 | 2017-05-18 | Neil R. Cashman | N-terminal epitopes in amyloid beta and conformationally-selective antibodies thereto |
JP2016047839A (ja) * | 2015-11-24 | 2016-04-07 | ヤンセン・サイエンシズ・アイルランド・ユーシー | アミロイド原性疾患の処置 |
US11066465B2 (en) | 2015-12-30 | 2021-07-20 | Kodiak Sciences Inc. | Antibodies and conjugates thereof |
ES2912064T3 (es) | 2016-02-19 | 2022-05-24 | Siwa Corp | Método y composición para tratar el cáncer, destruir las células cancerosas metastásicas y evitar la metástasis del cáncer usando anticuerpo para productos finales de glicación avanzada (AGE) |
CN109311975A (zh) * | 2016-04-15 | 2019-02-05 | Siwa有限公司 | 用于治疗神经退行性紊乱的抗age抗体 |
US11213585B2 (en) | 2016-06-23 | 2022-01-04 | Siwa Corporation | Vaccines for use in treating various diseases and disorders |
US20180125920A1 (en) | 2016-11-09 | 2018-05-10 | The University Of British Columbia | Methods for preventing and treating A-beta oligomer-associated and/or -induced diseases and conditions |
US10995151B1 (en) | 2017-01-06 | 2021-05-04 | Siwa Corporation | Methods and compositions for treating disease-related cachexia |
US10961321B1 (en) | 2017-01-06 | 2021-03-30 | Siwa Corporation | Methods and compositions for treating pain associated with inflammation |
US10925937B1 (en) | 2017-01-06 | 2021-02-23 | Siwa Corporation | Vaccines for use in treating juvenile disorders associated with inflammation |
US10858449B1 (en) | 2017-01-06 | 2020-12-08 | Siwa Corporation | Methods and compositions for treating osteoarthritis |
US10919957B2 (en) | 2017-04-13 | 2021-02-16 | Siwa Corporation | Humanized monoclonal advanced glycation end-product antibody |
MX2019015914A (es) | 2017-06-29 | 2020-08-06 | Univ Columbia | Anticuerpos quiméricos para el tratamiento de enfermedades por deposición de amiloide. |
US11382974B2 (en) | 2017-08-01 | 2022-07-12 | The Trustees Of Columbia University In The City Of New York | Methods and compositions for treatment of amyloid deposition diseases |
CA3073066A1 (en) | 2017-08-22 | 2019-02-28 | Biogen Ma Inc. | Pharmaceutical compositions containing anti-beta amyloid antibodies |
ES2812698T3 (es) | 2017-09-29 | 2021-03-18 | Probiodrug Ag | Inhibidores de glutaminil ciclasa |
US11518801B1 (en) | 2017-12-22 | 2022-12-06 | Siwa Corporation | Methods and compositions for treating diabetes and diabetic complications |
US20220031867A1 (en) | 2018-10-04 | 2022-02-03 | University Of Rochester | Glymphatic delivery by manipulating plasma osmolarity |
AR117453A1 (es) | 2018-12-20 | 2021-08-04 | Genentech Inc | Fc de anticuerpos modificados y métodos para utilizarlas |
CN111518206B (zh) * | 2019-02-01 | 2022-03-29 | 长春金赛药业有限责任公司 | 人源化抗Aβ单克隆抗体及其应用 |
JP2022527860A (ja) | 2019-04-02 | 2022-06-06 | ケンジョッケティ バイオテクノロジー,インク. | 排出ポンプ-癌抗原マルチ特異性抗体ならびにそれに関する組成物、試薬、キットおよび方法 |
WO2021072265A1 (en) | 2019-10-10 | 2021-04-15 | Kodiak Sciences Inc. | Methods of treating an eye disorder |
CN116529267A (zh) | 2020-06-04 | 2023-08-01 | 肯乔克蒂生物技术股份有限公司 | Abcg2外排泵-癌症抗原多特异性抗体及其相关组合物、试剂、试剂盒和方法 |
MX2023000949A (es) | 2020-07-23 | 2023-02-22 | Othair Prothena Ltd | Anticuerpos anti-beta-amiloide (abeta). |
TW202300517A (zh) | 2021-03-12 | 2023-01-01 | 美商美國禮來大藥廠 | 抗類澱粉β抗體及其用途 |
WO2022251048A1 (en) | 2021-05-24 | 2022-12-01 | Eli Lilly And Company | Anti-amyloid beta antibodies and uses thereof |
Family Cites Families (352)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6096318A (en) | 1973-05-07 | 2000-08-01 | The Ohio State University | Antigenically modified HCG polypeptides |
US4902506A (en) | 1983-07-05 | 1990-02-20 | The University Of Rochester | Immunogenic conjugates |
GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US5158769A (en) * | 1984-03-07 | 1992-10-27 | New York Blood Center, Inc. | Pre-S gene coded peptide hepatitis B immunogens, vaccines, diagnostics, and synthetic lipid vesicle carriers |
US5417986A (en) * | 1984-03-16 | 1995-05-23 | The United States Of America As Represented By The Secretary Of The Army | Vaccines against diseases caused by enteropathogenic organisms using antigens encapsulated within biodegradable-biocompatible microspheres |
US5208036A (en) | 1985-01-07 | 1993-05-04 | Syntex (U.S.A.) Inc. | N-(ω, (ω-1)-dialkyloxy)- and N-(ω, (ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
US4666829A (en) | 1985-05-15 | 1987-05-19 | University Of California | Polypeptide marker for Alzheimer's disease and its use for diagnosis |
US5618920A (en) | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
US4713366A (en) | 1985-12-04 | 1987-12-15 | The Ohio State University Research Foundation | Antigenic modification of polypeptides |
US5096706A (en) | 1986-03-25 | 1992-03-17 | National Research Development Corporation | Antigen-based treatment for adiposity |
US6548640B1 (en) * | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US5278049A (en) | 1986-06-03 | 1994-01-11 | Incyte Pharmaceuticals, Inc. | Recombinant molecule encoding human protease nexin |
US5231170A (en) | 1986-08-27 | 1993-07-27 | Paul Averback | Antibodies to dense microspheres |
US5220013A (en) | 1986-11-17 | 1993-06-15 | Scios Nova Inc. | DNA sequence useful for the detection of Alzheimer's disease |
US5187153A (en) | 1986-11-17 | 1993-02-16 | Scios Nova Inc. | Methods of treatment using Alzheimer's amyloid polypeptide derivatives |
US5223482A (en) | 1986-11-17 | 1993-06-29 | Scios Nova Inc. | Recombinant Alzheimer's protease inhibitory amyloid protein and method of use |
US4879213A (en) | 1986-12-05 | 1989-11-07 | Scripps Clinic And Research Foundation | Synthetic polypeptides and antibodies related to Epstein-Barr virus early antigen-diffuse |
US4912206A (en) | 1987-02-26 | 1990-03-27 | The United States Of America As Represented By The Department Of Health And Human Services | CDNA clone encoding brain amyloid of alzheimer's disease |
EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
US4883666A (en) | 1987-04-29 | 1989-11-28 | Massachusetts Institute Of Technology | Controlled drug delivery system for treatment of neural disorders |
US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
US5583112A (en) | 1987-05-29 | 1996-12-10 | Cambridge Biotech Corporation | Saponin-antigen conjugates and the use thereof |
US5057540A (en) | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
US5245015A (en) | 1991-04-26 | 1993-09-14 | Tanox Biosystems, Inc. | Monoclonal antibodies which neutralize HIV-1 through reaction with a conformational epitope in vitro |
US4912506A (en) * | 1987-06-10 | 1990-03-27 | Brother Kogyo Kabushiki Kaisha | Image recording apparatus having exposure unit |
US5869054A (en) | 1987-06-24 | 1999-02-09 | Autoimmune Inc. | Treatment of multiple sclerosis by oral administration of autoantigens |
US5641474A (en) | 1987-06-24 | 1997-06-24 | Autoimmune, Inc. | Prevention of autoimmune diseases by aerosol administration of autoantigens |
US5571499A (en) | 1987-06-24 | 1996-11-05 | Autoimmune, Inc. | Treatment of autoimmune diseases by aerosol administration of autoantigens |
US5849298A (en) | 1987-06-24 | 1998-12-15 | Autoimmune Inc. | Treatment of multiple sclerosis by oral administration of bovine myelin |
DE3854741T3 (de) | 1987-06-24 | 2002-08-14 | Autoimmune Inc | Behandlung von autoimmun-erkrankungen durch orale verabreichung von autoantigenen. |
US5571500A (en) | 1987-06-24 | 1996-11-05 | Autoimmune, Inc. | Treatment of autoimmune diseases through administration by inhalation of autoantigens |
US5645820A (en) | 1987-06-24 | 1997-07-08 | Autoimmune, Inc. | Treatment of autoimmune diseases by aerosol administration of autoantigens |
US5004697A (en) | 1987-08-17 | 1991-04-02 | Univ. Of Ca | Cationized antibodies for delivery through the blood-brain barrier |
US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
US5231000A (en) | 1987-10-08 | 1993-07-27 | The Mclean Hospital | Antibodies to A4 amyloid peptide |
CA1339014C (en) | 1987-10-08 | 1997-03-25 | Ronald E. Majocha | Antibodies to a4 amyloid peptide |
JP2518911B2 (ja) | 1987-10-23 | 1996-07-31 | 森永乳業株式会社 | c―fms癌原遺伝子の過剰発現によって特徴づけられた癌の処置用組成物および方法 |
US5089603A (en) * | 1989-06-21 | 1992-02-18 | Tanox Biosystems, Inc. | Antigenic epitopes present on membrane-bound but not secreted iga |
WO1989006689A1 (en) | 1988-01-13 | 1989-07-27 | The Mclean Hospital Corporation | Genetic constructs containing the alzheimer brain amyloid gene |
US4912094B1 (en) | 1988-06-29 | 1994-02-15 | Ribi Immunochem Research Inc. | Modified lipopolysaccharides and process of preparation |
US5576184A (en) | 1988-09-06 | 1996-11-19 | Xoma Corporation | Production of chimeric mouse-human antibodies with specificity to human tumor antigens |
WO1990005142A1 (en) | 1988-11-10 | 1990-05-17 | Imperial Cancer Research Technology Ltd. | Polypeptides |
IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5227159A (en) | 1989-01-31 | 1993-07-13 | Miller Richard A | Anti-idiotype antibodies reactive with shared idiotopes expressed by B cell lymphomas and autoantibodies |
US5262332A (en) | 1989-04-05 | 1993-11-16 | Brigham And Women's Hospital | Diagnostic method for Alzheimer's disease: examination of non-neural tissue |
WO1990012871A1 (en) | 1989-04-14 | 1990-11-01 | Research Foundation For Mental Hygiene, Inc. | Cerebrovascular amyloid protein-specific monoclonal antibody sv17-6e10 |
AU5525090A (en) | 1989-04-14 | 1990-11-16 | Research Foundation For Mental Hygiene, Inc. | Monoclonal antibody to amyloid peptide |
HU212924B (en) | 1989-05-25 | 1996-12-30 | Chiron Corp | Adjuvant formulation comprising a submicron oil droplet emulsion |
DE69033487T2 (de) | 1989-12-20 | 2000-06-29 | Autoimmune Inc | Behandlung von autoimmunkrankheiten durch verabreichung von autoantigenen in form von aerosol |
GB8928874D0 (en) * | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
EP1690935A3 (en) | 1990-01-12 | 2008-07-30 | Abgenix, Inc. | Generation of xenogeneic antibodies |
JPH05508621A (ja) | 1990-03-02 | 1993-12-02 | オートイミューン インク | 自己抗原の経口投与による自己免疫疾患のダウンコントロール |
CA2079880A1 (en) | 1990-04-24 | 1991-10-25 | William E. Van Nostrand | Purification, detection and methods of use of protease nexin-2 |
ATE153534T1 (de) | 1990-04-27 | 1997-06-15 | John Mcmichael | Verfahren und zusammensetzung zur behandlung von erkrankungen des zns hervorgerufen durch abnormales beta-amyloid-protein |
US5753624A (en) | 1990-04-27 | 1998-05-19 | Milkhaus Laboratory, Inc. | Materials and methods for treatment of plaquing disease |
GB9009548D0 (en) | 1990-04-27 | 1990-06-20 | Celltech Ltd | Chimeric antibody and method |
CA2085127C (en) | 1990-06-15 | 2002-12-10 | Barbara Cordell | Transgenic non-human mammal displaying the amyloid-forming pathology of alzheimer's disease |
WO1991019795A1 (en) | 1990-06-19 | 1991-12-26 | Immuvax | Nonpathogenic variant virus |
GB9014932D0 (en) | 1990-07-05 | 1990-08-22 | Celltech Ltd | Recombinant dna product and method |
US5780587A (en) | 1990-08-24 | 1998-07-14 | President And Fellows Of Harvard College | Compounds and methods for inhibiting β-protein filament formation and neurotoxicity |
NZ239643A (en) | 1990-09-17 | 1996-05-28 | North American Vaccine Inc | Vaccine containing bacterial polysaccharide protein conjugate and adjuvant (c-nd-che-a-co-b-r) with a long chain alkyl group. |
US5702906A (en) | 1990-09-25 | 1997-12-30 | Genentech, Inc. | Antibodies to neurotrophic factor-4 (NT-4) |
JPH06502071A (ja) | 1990-09-28 | 1994-03-10 | ジ・アップジョン・カンパニー | アルツハイマーのアミロイド前駆遺伝子を有するトランスジェニック動物 |
ATE175118T1 (de) | 1990-10-05 | 1999-01-15 | Medarex Inc | Gezielte immunostimulierung mit bispezifischen stoffen |
IL99754A (en) | 1990-10-15 | 1996-08-04 | Autoimmune Inc | Pharmaceutical preparation containing autoantib or particle or analogue for the treatment of autoimmune arthritis and multiple sclerosis |
GB9023352D0 (en) | 1990-10-26 | 1990-12-05 | Lynxvale Ltd | Vaccinia vectors,vaccinia genes and expression products thereof |
US5877015A (en) | 1991-01-21 | 1999-03-02 | Imperial College Of Science, Technology Of Medicine | APP770 mutant in alzheimer's disease |
EP0501882B1 (fr) | 1991-03-01 | 2000-07-12 | Merial | Procédé d'immunoneutralisation anti-LHRM des animaux domestiques mâles non castrés et peptide pour cela |
US5192753A (en) | 1991-04-23 | 1993-03-09 | Mcgeer Patrick L | Anti-rheumatoid arthritic drugs in the treatment of dementia |
JPH06500128A (ja) | 1991-05-08 | 1994-01-06 | シュバイツ・ゼルム―・ウント・インプフィンスティテュート・ベルン | 免疫刺激及び免疫増強性再構成インフルエンザウイロソーム及びそれを含有するワクチン |
WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
LU91067I2 (fr) * | 1991-06-14 | 2004-04-02 | Genentech Inc | Trastuzumab et ses variantes et dérivés immuno chimiques y compris les immotoxines |
US5672805A (en) | 1991-07-18 | 1997-09-30 | The Regents Of The University Of California | Transgenic mice expressing the neurotoxic C-terminus of β-amyloid precursor protein |
US5434050A (en) | 1991-08-13 | 1995-07-18 | Regents Of The University Of Minnesota | Labelled β-amyloid peptide and methods of screening for Alzheimer's disease |
US5837268A (en) | 1991-10-16 | 1998-11-17 | University Of Saskatchewan | GnRH-leukotoxin chimeras |
JPH07503132A (ja) | 1991-12-17 | 1995-04-06 | ジェンファーム インターナショナル,インコーポレイティド | 異種抗体を産生することができるトランスジェニック非ヒト動物 |
WO1993014200A1 (en) | 1992-01-07 | 1993-07-22 | Tsi Corporation | Transgenic animal models for alzheimer's disease |
US5679348A (en) | 1992-02-03 | 1997-10-21 | Cedars-Sinai Medical Center | Immunotherapy for recurrent HSV infections |
EP1958646A1 (en) | 1992-02-11 | 2008-08-20 | Henry M. Jackson Foundation For The Advancement Of Military Medicine | Dual carrier immunogenic construct |
DK0627933T3 (da) | 1992-02-28 | 2003-03-24 | Autoimmune Inc | Bystander-suppression af autoimmune sygdomme |
US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
US5604102A (en) | 1992-04-15 | 1997-02-18 | Athena Neurosciences, Inc. | Methods of screening for β-amyloid peptide production inhibitors |
US5441870A (en) | 1992-04-15 | 1995-08-15 | Athena Neurosciences, Inc. | Methods for monitoring cellular processing of β-amyloid precursor protein |
US5851787A (en) | 1992-04-20 | 1998-12-22 | The General Hospital Corporation | Nucleic acid encoding amyloid precursor-like protein and uses thereof |
CA2118508A1 (en) | 1992-04-24 | 1993-11-11 | Elizabeth S. Ward | Recombinant production of immunoglobulin-like domains in prokaryotic cells |
GB9209118D0 (en) | 1992-04-28 | 1992-06-10 | Sb 120 Amsterdam Bv | Vaccine compositions |
WO1993025210A1 (en) | 1992-06-18 | 1993-12-23 | President And Fellows Of Harvard College | Diphtheria toxin vaccines |
SG49909A1 (en) | 1992-06-25 | 1998-06-15 | Smithkline Beecham Biolog | Vaccine composition containing adjuvants |
US5766846A (en) | 1992-07-10 | 1998-06-16 | Athena Neurosciences | Methods of screening for compounds which inhibit soluble β-amyloid peptide production |
US5837672A (en) | 1992-07-10 | 1998-11-17 | Athena Neurosciences, Inc. | Methods and compositions for the detection of soluble β-amyloid peptide |
US6610493B1 (en) | 1993-06-17 | 2003-08-26 | Brigham And Women's Hospital | Screening compounds for the ability to alter the production of amyloid-β peptide |
WO1994001772A1 (en) | 1992-07-13 | 1994-01-20 | The Children's Medical Center Corporation | SCREEN FOR ALZHEIMER'S DISEASE THERAPEUTICS BASED ON β-AMYLOID PRODUCTION |
IL102687A (en) | 1992-07-30 | 1997-06-10 | Yeda Res & Dev | Conjugates of poorly immunogenic antigens and synthetic pepide carriers and vaccines comprising them |
DE69322645T2 (de) | 1992-07-31 | 1999-05-20 | Medeva Holdings Bv | Expression rekombinanter fusionsproteine in attenuierten bakterien |
HUT71860A (en) | 1992-08-27 | 1996-02-28 | Deakin Res Ltd | Retro-, inverso-, and retro-inverso synthetic peptide analogues |
US5958883A (en) | 1992-09-23 | 1999-09-28 | Board Of Regents Of The University Of Washington Office Of Technology | Animal models of human amyloidoses |
AU5358494A (en) | 1992-10-13 | 1994-05-09 | Duke University | Method of inhibiting binding of amyloid precursor protein to beta-amyloid protein |
US5605811A (en) | 1992-10-26 | 1997-02-25 | Athena Neurosciences, Inc. | Methods and compositions for monitoring cellular processing of beta-amyloid precursor protein |
EP1298436B1 (en) | 1992-10-26 | 2010-07-14 | Elan Pharmaceuticals, Inc. | Methods for the identification of Beta-amyloid peptide (BAP) release inhibitor compounds |
US5972336A (en) | 1992-11-03 | 1999-10-26 | Oravax Merieux Co. | Urease-based vaccine against helicobacter infection |
US6210671B1 (en) | 1992-12-01 | 2001-04-03 | Protein Design Labs, Inc. | Humanized antibodies reactive with L-selectin |
ATE372783T1 (de) | 1993-01-22 | 2007-09-15 | Sloan Kettering Inst Cancer | Gangliosid-klh-konjugatimpfstoffe mit qs-21 zur verzögerung des wiederauftretens eines melanoms |
US5955317A (en) | 1993-01-25 | 1999-09-21 | Takeda Chemical Industries, Ltd. | Antibodies to β-amyloids or their derivatives and use thereof |
EP0683234B2 (en) | 1993-01-25 | 2007-06-06 | Takeda Chemical Industries, Ltd. | Antibody against beta-amyloid or their derivative and use thereof |
US5358708A (en) | 1993-01-29 | 1994-10-25 | Schering Corporation | Stabilization of protein formulations |
US5472693A (en) | 1993-02-16 | 1995-12-05 | The Dow Chemical Company | Family of anti-carcinoembryonic antigen chimeric antibodies |
DE614989T1 (de) | 1993-02-17 | 1995-09-28 | Morphosys Proteinoptimierung | Verfahren für in vivo Selektion von Ligandenbindende Proteine. |
DE69435075T2 (de) | 1993-03-17 | 2009-02-19 | The Government Of The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Immunogene chimäre umfassend nucleinsäuresequenzen, die signalsequenzpeptide des endoplasmatischen reticulums und mindestens ein anderes peptid codieren, deren verwendung in impfstoffen und zur behandlung von krankheiten |
JP3880063B2 (ja) | 1993-03-18 | 2007-02-14 | シティミューン サイエンシーズ,インコーポレイテッド | 生物学的に活性な因子の毒性を低減させる組成物および方法 |
CN1087176C (zh) | 1993-03-23 | 2002-07-10 | 史密斯克莱·比奇曼生物公司 | 含有3-o脱酰基单磷酰脂a的疫苗制剂 |
IT1270939B (it) | 1993-05-11 | 1997-05-26 | Angeletti P Ist Richerche Bio | Procedimento per la preparazione di immunogeni e reagenti diagnostici,e immunogeni e reagenti diagnostici cosi' ottenibili. |
EP0705109B2 (en) * | 1993-05-25 | 2004-01-02 | American Cyanamid Company | Adjuvants for vaccines against respiratory syncytial virus |
WO1994028412A1 (en) | 1993-05-28 | 1994-12-08 | The Miriam Hospital | Composition and method for in vivo imaging of amyloid deposits |
ATE212378T1 (de) | 1993-06-04 | 2002-02-15 | Whitehead Biomedical Inst | Stressproteine und ihre verwendung |
US5464823A (en) | 1993-07-20 | 1995-11-07 | The Regents Of The University Of California | Mammalian antibiotic peptides |
EP0712442B1 (en) | 1993-07-30 | 2002-03-27 | Medeva Holdings B.V. | Vaccine compositions |
EP0664814A1 (en) | 1993-08-18 | 1995-08-02 | MorphoSys AG | Lipopolysaccharide-binding and neutralizing peptides |
DK96493D0 (da) | 1993-08-26 | 1993-08-26 | Mouritsen Og Elsner Aps | Fremgangsmaade til at inducere antistofresponser mod selvproteiner og autovaccine fremstillet ved fremgangsmaaden |
CA2169635C (en) | 1993-08-26 | 2002-11-12 | Dennis A. Carson | Method, compositions and devices for administration of naked polynucleotides which encode biologically active peptides |
AU707083B2 (en) | 1993-08-26 | 1999-07-01 | Bavarian Nordic Inc. | Inducing antibody response against self-proteins with the aid of foreign T-cell epitopes |
WO1995006407A1 (en) | 1993-08-30 | 1995-03-09 | The Regents Of The University Of California | Novel component of amyloid in alzheimer's disease and methods for use of same |
ES2236693T3 (es) | 1993-09-07 | 2005-07-16 | Smithkline Beecham Corporation | Anticuerpos recombinantes contra il4 utiles en el tratamiento de afecciones mediadas por il4. |
US5652334A (en) | 1993-09-08 | 1997-07-29 | City Of Hope | Method for design of substances that enhance memory and improve the quality of life |
US5385887A (en) | 1993-09-10 | 1995-01-31 | Genetics Institute, Inc. | Formulations for delivery of osteogenic proteins |
DE69435171D1 (de) | 1993-09-14 | 2009-01-08 | Pharmexa Inc | Pan dr-bindeproteinen zur erhöhung der immunantwort |
US5470951A (en) | 1993-09-29 | 1995-11-28 | City Of Hope | Peptides for antagonizing the effects of amyloid βprotein |
US5858981A (en) * | 1993-09-30 | 1999-01-12 | University Of Pennsylvania | Method of inhibiting phagocytosis |
JPH09506170A (ja) | 1993-10-20 | 1997-06-17 | デューク・ユニヴァーシティ | β‐アミロイドペプチドに物質を結合する方法 |
AU7979094A (en) | 1993-10-22 | 1995-05-08 | Genentech Inc. | Methods and compositions for microencapsulation of adjuvants |
US5744368A (en) | 1993-11-04 | 1998-04-28 | Research Foundation Of State University Of New York | Methods for the detection of soluble amyloid β-protein (βAP) or soluble transthyretin (TTR) |
US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
US5434170A (en) | 1993-12-23 | 1995-07-18 | Andrulis Pharmaceuticals Corp. | Method for treating neurocognitive disorders |
EP0742831B1 (en) * | 1994-01-27 | 2004-09-29 | The Regents Of The University Of Minnesota | Transgenic non-human mammals with progressive neurologic disease |
US5877399A (en) | 1994-01-27 | 1999-03-02 | Johns Hopkins University | Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease |
WO1995020979A1 (en) | 1994-02-03 | 1995-08-10 | The Picower Institute For Medical Research | Compositions and methods for advanced glycosylation endproduct-mediated modulation of amyloidosis |
AUPM411994A0 (en) | 1994-02-25 | 1994-03-24 | Deakin Research Limited | Epitopes |
US5795954A (en) | 1994-03-04 | 1998-08-18 | Genentech, Inc. | Factor VIIa inhibitors from Kunitz domain proteins |
US6270757B1 (en) * | 1994-04-21 | 2001-08-07 | Genetics Institute, Inc. | Formulations for IL-11 |
US6372716B1 (en) * | 1994-04-26 | 2002-04-16 | Genetics Institute, Inc. | Formulations for factor IX |
JP3064013B2 (ja) | 1994-05-25 | 2000-07-12 | ジョン マクマイケル, | 斑形成疾患の治療のための方法及び材料 |
US5622701A (en) | 1994-06-14 | 1997-04-22 | Protein Design Labs, Inc. | Cross-reacting monoclonal antibodies specific for E- and P-selectin |
US5798100A (en) | 1994-07-06 | 1998-08-25 | Immunomedics, Inc. | Multi-stage cascade boosting vaccine |
US6417178B1 (en) * | 1994-07-19 | 2002-07-09 | University Of Pittsburgh | Amyloid binding nitrogen-linked compounds for the antemortem diagnosis of alzheimer's disease, in vivo imaging and prevention of amyloid deposits |
WO1996003144A1 (en) | 1994-07-27 | 1996-02-08 | The Council Of The Queensland Institute Of Medical Research | Polyepitope vaccines |
WO1996008565A2 (en) | 1994-09-16 | 1996-03-21 | Cancer Research Fund Of Contra Costa | RECOMBINANT PEPTIDES DERIVED FROM THE Mc3 ANTI-BA46 ANTIBODY, METHODS OF USE THEREOF, AND METHODS OF HUMANIZING ANTIBODY PEPTIDES |
US5872005A (en) | 1994-11-03 | 1999-02-16 | Cell Genesys Inc. | Packaging cell lines for adeno-associated viral vectors |
US6114133A (en) | 1994-11-14 | 2000-09-05 | Elan Pharmaceuticals, Inc. | Methods for aiding in the diagnosis of Alzheimer's disease by measuring amyloid-β peptide (x-≧41) |
US5589154A (en) * | 1994-11-22 | 1996-12-31 | Rutgers, The State University Of New Jersey | Methods for the prevention or treatment of vascular hemorrhaging and Alzheimer's disease |
US5688651A (en) | 1994-12-16 | 1997-11-18 | Ramot University Authority For Applied Research And Development Ltd. | Prevention of protein aggregation |
EP0820299B1 (en) | 1995-02-06 | 2002-04-24 | Genetics Institute, Inc. | Formulations for il-12 |
US5786180A (en) | 1995-02-14 | 1998-07-28 | Bayer Corporation | Monoclonal antibody 369.2B specific for β A4 peptide |
US5624937A (en) | 1995-03-02 | 1997-04-29 | Eli Lilly And Company | Chemical compounds as inhibitors of amyloid beta protein production |
US6303567B1 (en) | 1995-03-14 | 2001-10-16 | Praecis Pharmaceuticals, Inc . | Modulators of β-amyloid peptide aggregation comprising D-amino acids |
US5817626A (en) | 1995-03-14 | 1998-10-06 | Praecis Pharmaceuticals Incorporated | Modulators of beta-amyloid peptide aggregation |
US5854215A (en) | 1995-03-14 | 1998-12-29 | Praecis Pharmaceuticals Incorporated | Modulators of β-amyloid peptide aggregation |
ES2175083T3 (es) | 1995-03-14 | 2002-11-16 | Praecis Pharm Inc | Moduladores de la agregacion de amiloides. |
EP0871755A1 (en) | 1995-03-23 | 1998-10-21 | Cantab Pharmaceuticals Research Limited | Vectors for gene delivery |
US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
US6121022A (en) | 1995-04-14 | 2000-09-19 | Genentech, Inc. | Altered polypeptides with increased half-life |
UA56132C2 (uk) | 1995-04-25 | 2003-05-15 | Смітклайн Бічем Байолоджікалс С.А. | Композиція вакцини (варіанти), спосіб стабілізації qs21 відносно гідролізу (варіанти), спосіб приготування композиції вакцини |
CA2222055A1 (en) | 1995-05-23 | 1996-11-28 | Morphosys Gesellschaft Fur Proteinoptimierung Mbh | Multimeric proteins |
WO1996039176A1 (en) | 1995-06-05 | 1996-12-12 | Brigham & Women's Hospital | USE OF ORAL TOLERANCE TO SUPPRESS BOTH Th1 AND Th2 IMMUNE RESPONSES AND TO SUPPRESS ANTIBODY PRODUCTION |
US5948763A (en) | 1995-06-07 | 1999-09-07 | New York University | Peptides and pharmaceutical compositions thereof for treatment of disorders or diseases associated with abnormal protein folding into amyloid or amyloid-like deposits |
CA2221986A1 (en) | 1995-06-07 | 1996-12-19 | Athena Neurosciences, Inc. | Method for identifying alzheimer's disease therapeutics using transgenic animal models |
US5910427A (en) | 1995-06-22 | 1999-06-08 | La Jolla Institute For Allergy And Immunology | Antigen non-specific glycosylation inhibiting factor derivatives |
PT750907E (pt) | 1995-06-30 | 2002-08-30 | American Cyanamid Co | Formulacoes de vacinas estaveis para administracao parenterica metodo para a sua utilizacao e processo para a sua preparacao |
ATE305039T1 (de) | 1995-07-07 | 2005-10-15 | Darwin Molecular Corp | Auf chromosom 1 lokalisiertes gen dessen genprodukt mit der alzheimerschen krankheit assoziiert ist. |
US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
AUPN443995A0 (en) | 1995-07-27 | 1995-08-17 | Csl Limited | Papillomavirus polyprotein |
US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
ATE219517T1 (de) | 1995-08-18 | 2002-07-15 | Morphosys Ag | Protein-/(poly)peptidbibliotheken |
US5824322A (en) | 1995-08-21 | 1998-10-20 | Cytrx Corporation | Compositions and methods for growth promotion |
DE69632056T2 (de) | 1995-09-14 | 2004-12-30 | The Regents Of The University Of California, Oakland | Für natives prp-sc spezifische antikörper |
US5731284A (en) * | 1995-09-28 | 1998-03-24 | Amgen Inc. | Method for treating Alzheimer's disease using glial line-derived neurotrophic factor (GDNF) protein product |
WO1997013855A1 (en) | 1995-10-10 | 1997-04-17 | Novartis Ag | Melanoma-associated protein |
US5985242A (en) | 1995-10-27 | 1999-11-16 | Praecis Pharmaceuticals, Inc. | Modulators of β-amyloid peptide aggregation comprising D-amino acids |
US5750361A (en) | 1995-11-02 | 1998-05-12 | The Regents Of The University Of California | Formation and use of prion protein (PRP) complexes |
EP0859959B1 (en) | 1995-11-10 | 2003-08-06 | ELAN CORPORATION, Plc | Peptides which enhance transport across tissues and methods of identifying and using the same |
WO1997018855A1 (en) | 1995-11-21 | 1997-05-29 | Eduard Naumovich Lerner | Device for enhanced delivery of biologically active substances and compounds in an organism |
EP0866805A1 (en) | 1995-12-12 | 1998-09-30 | Karolinska Innovations AB | PEPTIDE BINDING THE KLVFF-SEQUENCE OF AMYLOID $g(b) |
US6015662A (en) * | 1996-01-23 | 2000-01-18 | Abbott Laboratories | Reagents for use as calibrators and controls |
US5770700A (en) | 1996-01-25 | 1998-06-23 | Genetics Institute, Inc. | Liquid factor IX formulations |
US6096313A (en) | 1996-02-09 | 2000-08-01 | Ludwig Institute For Cancer Research | Compositions containing immunogenic molecules and granulocyte-macrophage colony stimulating factor, as an adjuvant |
JP2000505306A (ja) | 1996-02-26 | 2000-05-09 | モルフォシス・アクチェンゲゼルシャフト | 2つまたはそれ以上の相互作用性(ポリ)ペプチドをコードする核酸配列の新規同定方法 |
US6150091A (en) | 1996-03-06 | 2000-11-21 | Baylor College Of Medicine | Direct molecular diagnosis of Friedreich ataxia |
HUP9902438A3 (en) | 1996-03-29 | 2000-03-28 | Bayer Ag | Parapoxvirus vectors |
EP0954324A4 (en) | 1996-04-03 | 2000-11-02 | Anergen Inc | CYCLIC PEPTID VACCINES FOR DIABETES TREATMENT AND PREVENTION |
WO1997040147A1 (en) | 1996-04-19 | 1997-10-30 | The Government Of The United States Of America, Represented By The Secretary Of The Department Of Health And Human Services | Antigenically reactive regions of the hepatitis a virus polyprotein |
US6284533B1 (en) | 1996-05-01 | 2001-09-04 | Avant Immunotherapeutics, Inc. | Plasmid-based vaccine for treating atherosclerosis |
EP0938506B1 (en) | 1996-07-16 | 2003-11-05 | Plückthun, Andreas, Prof. Dr. | Immunoglobulin superfamily domains and fragments with increased solubility |
CA2262006A1 (en) | 1996-07-26 | 1998-02-05 | Sloan-Kettering Institute For Cancer Research | Method and reagents for genetic immunization |
US7147851B1 (en) | 1996-08-15 | 2006-12-12 | Millennium Pharmaceuticals, Inc. | Humanized immunoglobulin reactive with α4β7 integrin |
CA2183901A1 (en) | 1996-08-22 | 1998-02-23 | Johanna E. Bergmann | Targets for therapy and diagnosis of alzheimer's disease and down syndrome in humans |
GB9617616D0 (en) | 1996-08-22 | 1996-10-02 | Osteometer Biotech As | Assaying protein fragments in body fluids |
EP1586584A1 (en) | 1996-08-27 | 2005-10-19 | Praecis Pharmaceuticals Incorporated | Modulators of beta-amyloid peptide aggregation comprising D-amino acids |
US6057367A (en) | 1996-08-30 | 2000-05-02 | Duke University | Manipulating nitrosative stress to kill pathologic microbes, pathologic helminths and pathologically proliferating cells or to upregulate nitrosative stress defenses |
US6797495B2 (en) | 1996-11-05 | 2004-09-28 | The Regents Of The University Of California | Somatic cells with ablated PrP gene and methods of use |
US6022859A (en) | 1996-11-15 | 2000-02-08 | Wisconsin Alumni Research Foundation | Inhibitors of β-amyloid toxicity |
WO1998022120A1 (en) | 1996-11-19 | 1998-05-28 | The Wistar Institute Of Anatomy & Biology | Diagnostic and therapeutic reagents for alzheimer's disease |
US6962984B2 (en) | 1996-12-05 | 2005-11-08 | Nihon University | IgA nephropathy-related DNA |
US20030068316A1 (en) | 1997-02-05 | 2003-04-10 | Klein William L. | Anti-ADDL antibodies and uses thereof |
US6218506B1 (en) * | 1997-02-05 | 2001-04-17 | Northwestern University | Amyloid β protein (globular assembly and uses thereof) |
US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
CA2278547A1 (en) | 1997-03-03 | 1998-09-11 | Boehringer Ingelheim Pharmaceuticals, Inc. | Small molecules useful in the treatment of inflammatory disease |
US5798102A (en) | 1997-03-04 | 1998-08-25 | Milkhaus Laboratory, Inc. | Treatment of cardiomyopathy |
US6057098A (en) * | 1997-04-04 | 2000-05-02 | Biosite Diagnostics, Inc. | Polyvalent display libraries |
US8173127B2 (en) | 1997-04-09 | 2012-05-08 | Intellect Neurosciences, Inc. | Specific antibodies to amyloid beta peptide, pharmaceutical compositions and methods of use thereof |
US20020086847A1 (en) * | 1997-04-09 | 2002-07-04 | Mindset Biopharmaceuticals (Usa) | Recombinant antibodies specific for beta-amyloid ends, DNA encoding and methods of use thereof |
NZ337765A (en) | 1997-04-09 | 2001-09-28 | Mindset Biopharmaceuticals Usa | Recombinant antibodies having specificity for beta-amyloid N-terminus and C-terminus and use in treating Alzheimer's Disease |
US6787319B2 (en) * | 1997-04-16 | 2004-09-07 | American Home Products Corp. | β-amyloid peptide-binding proteins and polynucleotides encoding the same |
AU7690898A (en) * | 1997-05-20 | 1998-12-11 | Ottawa Civic Hospital Loeb Research Institute | Vectors and methods for immunization or therapeutic protocols |
AU740284B2 (en) | 1997-06-13 | 2001-11-01 | Genentech Inc. | Stabilized antibody formulation |
WO1999000150A2 (en) | 1997-06-27 | 1999-01-07 | Regents Of The University Of California | Drug targeting of a peptide radiopharmaceutical through the primate blood-brain barrier in vivo with a monoclonal antibody to the human insulin receptor |
IT1293511B1 (it) | 1997-07-30 | 1999-03-01 | Gentili Ist Spa | Anticorpi monoclonali catalitici ad attivita' proteasica per la lisi selettiva della componente proteica di placche e aggregati correlati |
DE69842048D1 (de) | 1997-08-01 | 2011-01-27 | Max Planck Gesellschaft | Zusammensetzung und verfahren zum nachweis von krankheiten in zusammenhang mit der bildung von amyloid-ähnlichen fibrillen oder protein-aggregaten |
JP2002501721A (ja) | 1997-08-01 | 2002-01-22 | モルフォシス・アクチェンゲゼルシャフト | 多量体(ポリ)ペプチドコンプレックスのメンバーをコードする核酸配列を同定するための新規方法およびファージ |
ATE435661T1 (de) | 1997-08-29 | 2009-07-15 | Antigenics Inc | Adjuvant qs-21 enthaltende zusammensetzungen mit polysorbate oder cyclodextrin als hilfsmittel |
US6175057B1 (en) | 1997-10-08 | 2001-01-16 | The Regents Of The University Of California | Transgenic mouse model of alzheimer's disease and cerebral amyloid angiopathy |
EP0921189B1 (en) * | 1997-11-14 | 2005-01-12 | Sankyo Company Limited | Transgenic animal allergy models and methods for their use |
US6743427B1 (en) * | 1997-12-02 | 2004-06-01 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
US6923964B1 (en) | 1997-12-02 | 2005-08-02 | Neuralab Limited | Active immunization of AScr for prion disorders |
US7179892B2 (en) * | 2000-12-06 | 2007-02-20 | Neuralab Limited | Humanized antibodies that recognize beta amyloid peptide |
US6750324B1 (en) * | 1997-12-02 | 2004-06-15 | Neuralab Limited | Humanized and chimeric N-terminal amyloid beta-antibodies |
US6761888B1 (en) | 2000-05-26 | 2004-07-13 | Neuralab Limited | Passive immunization treatment of Alzheimer's disease |
US6710226B1 (en) * | 1997-12-02 | 2004-03-23 | Neuralab Limited | Transgenic mouse assay to determine the effect of Aβ antibodies and Aβ Fragments on alzheimer's disease characteristics |
US20080050367A1 (en) | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
US6787523B1 (en) * | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
US7790856B2 (en) | 1998-04-07 | 2010-09-07 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize beta amyloid peptide |
US6913745B1 (en) * | 1997-12-02 | 2005-07-05 | Neuralab Limited | Passive immunization of Alzheimer's disease |
US7964192B1 (en) * | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
TWI239847B (en) | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
US7588766B1 (en) | 2000-05-26 | 2009-09-15 | Elan Pharma International Limited | Treatment of amyloidogenic disease |
DE1033998T1 (de) | 1997-12-03 | 2001-05-23 | Brigham And Women S Hospital B | Methode zur unterdrückung von beta-amyloid-verwandten veränderungen in alzheimer |
EP1036562A1 (en) | 1997-12-03 | 2000-09-20 | Fujisawa Pharmaceutical Co., Ltd. | Soft-pellet drug and process for the preparation thereof |
FR2777015B3 (fr) | 1998-02-23 | 2000-09-15 | Financ De Biotechnologie | Procede et moyens pour l'obtention de modeles cellulaires et animaux de maladies neurodegeneratives |
US6194551B1 (en) * | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
US6528624B1 (en) * | 1998-04-02 | 2003-03-04 | Genentech, Inc. | Polypeptide variants |
US20050059802A1 (en) * | 1998-04-07 | 2005-03-17 | Neuralab Ltd | Prevention and treatment of amyloidogenic disease |
US20050059591A1 (en) * | 1998-04-07 | 2005-03-17 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
ES2230848T3 (es) | 1998-04-28 | 2005-05-01 | Smithkline Beecham Corporation | Anticuerpos monoclonales con inmunogenicidad reducida. |
NO314086B1 (no) | 1998-05-08 | 2003-01-27 | Gemvax As | Peptider og farmasöytiske sammensetninger inneholdende disse, nukleinsyresekvenser som koder for slike peptider, plasmider og virusvektoreromfattende slike DNA-sekvenser samt anvendelse av disse for fremstilling avfarmasöytiske preparater til |
EP1080110A2 (en) | 1998-05-19 | 2001-03-07 | Yeda Research And Development Co. Ltd. | Use of activated t cells, nervous system-specific antigens for treating disorders of the nevrous system |
AU4007599A (en) | 1998-05-21 | 1999-12-06 | University Of Tennessee Research Corporation, The | Methods for amyloid removal using anti-amyloid antibodies |
US20030147882A1 (en) | 1998-05-21 | 2003-08-07 | Alan Solomon | Methods for amyloid removal using anti-amyloid antibodies |
US6432710B1 (en) | 1998-05-22 | 2002-08-13 | Isolagen Technologies, Inc. | Compositions for regenerating tissue that has deteriorated, and methods for using such compositions |
US6727349B1 (en) * | 1998-07-23 | 2004-04-27 | Millennium Pharmaceuticals, Inc. | Recombinant anti-CCR2 antibodies and methods of use therefor |
HUP0103976A3 (en) | 1998-10-05 | 2008-04-28 | Pharmexa As | Novel methods for therapeutic vaccination |
WO2000023082A1 (en) | 1998-10-19 | 2000-04-27 | Yeda Research And Development Co. Ltd. | Treatment of systemic lupus erythematosus by down-regulating the autoimmune response to autoantigens |
US7112661B1 (en) | 1998-10-30 | 2006-09-26 | The Research Foundation Of State University Of New York | Variable heavy chain and variable light chain regions of antibodies to human platelet glycoprotein Ib alpha |
GB2348203B (en) | 1998-11-04 | 2002-06-19 | Imp College Innovations Ltd | Solube beta-forms of prion proteins, methods of preparation and use |
CN101362518A (zh) | 1999-01-19 | 2009-02-11 | 法玛西雅厄普约翰美国公司 | γ-照射消毒的聚乙烯包装 |
JP2002535289A (ja) | 1999-01-22 | 2002-10-22 | ドウアリング,マシユー・ジヨン | 神経疾患のワクチン媒介治療 |
US7629311B2 (en) | 1999-02-24 | 2009-12-08 | Edward Lewis Tobinick | Methods to facilitate transmission of large molecules across the blood-brain, blood-eye, and blood-nerve barriers |
US7282570B2 (en) * | 1999-04-20 | 2007-10-16 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
IL146009A0 (en) | 1999-05-05 | 2002-07-25 | Neurochem Inc | Stereoselective antifibrillogenic peptides and peptidomimetics thereof |
US6787637B1 (en) | 1999-05-28 | 2004-09-07 | Neuralab Limited | N-Terminal amyloid-β antibodies |
UA81216C2 (en) | 1999-06-01 | 2007-12-25 | Prevention and treatment of amyloid disease | |
AR024558A1 (es) | 1999-06-01 | 2002-10-16 | Neuralab Ltd | Composiciones del peptido a-beta y procesos para producir las mismas |
EP1409654B1 (en) | 1999-06-16 | 2008-08-20 | Boston Biomedical Research Institute | Immunological control of beta-amyloid levels in vivo |
IL147599A0 (en) | 1999-07-15 | 2002-08-14 | Genetics Inst | Formulations for il-11 |
AU6524500A (en) | 1999-08-04 | 2001-03-05 | Northwestern University | Amyloid beta protein (globular assembly and uses thereof) |
US6919075B1 (en) | 1999-09-03 | 2005-07-19 | Ramot At Tel Aviv University Ltd. | Bacteriophage displaying aβ epitopes and method of use |
US6294171B2 (en) | 1999-09-14 | 2001-09-25 | Milkhaus Laboratory, Inc. | Methods for treating disease states comprising administration of low levels of antibodies |
US6824780B1 (en) | 1999-10-29 | 2004-11-30 | Genentech, Inc. | Anti-tumor antibody compositions and methods of use |
US20020094335A1 (en) | 1999-11-29 | 2002-07-18 | Robert Chalifour | Vaccine for the prevention and treatment of alzheimer's and amyloid related diseases |
KR20080059676A (ko) | 1999-11-29 | 2008-06-30 | 뉴로겜 인터내셔널 리미티드 | 알츠하이머 및 아밀로이드 관련 질병의 예방 및 치료용백신 |
WO2001042306A2 (en) | 1999-12-08 | 2001-06-14 | Mindset Biopharmaceuticals (Usa), Inc. | Chimeric peptides (short b-cell epitope joined to a t-cell epitope) and their use for immunization |
US6399314B1 (en) * | 1999-12-29 | 2002-06-04 | American Cyanamid Company | Methods of detection of amyloidogenic proteins |
ME00183B (me) | 2000-02-21 | 2011-02-10 | Pharmexa As | Novi postupak za deregulaciju amiloida |
CZ20022748A3 (cs) | 2000-02-21 | 2004-03-17 | Pharmexa A/S | Nová metoda regulace obsahu amyloidu |
AU4178601A (en) * | 2000-02-24 | 2001-09-03 | Univ Washington | Humanized antibodies that sequester abeta peptide |
CA2404237C (en) | 2000-04-05 | 2010-01-26 | University Of Tennessee Research Corporation | Methods of investigating, diagnosing, and treating amyloidosis |
DE60134499D1 (de) | 2000-04-13 | 2008-07-31 | Corixa Corp | Immunostimulierende zusammnensetzungen die aminoalkyl glucosaminidephosphat und qs-21 enthalten |
IL152625A0 (en) | 2000-05-22 | 2003-06-24 | Univ New York | SYNTHETIC IMMUNOGENIC BUT NON-AMYLOIDOGENIC PEPTIDES HOMOLOGOUS TO AMYLOID beta FOR INDUCTION OF AN IMMUNE RESPONSE TO AMYLOID beta AND AMYLOID DEPOSITS |
CA2414772C (en) | 2000-07-07 | 2011-06-28 | Jan Naslund | Prevention and treatment of alzheimer's disease |
EP1172378A1 (en) | 2000-07-12 | 2002-01-16 | Richard Dr. Dodel | Human beta-amyloid antibody and use thereof for treatment of alzheimer's disease |
US20020009445A1 (en) * | 2000-07-12 | 2002-01-24 | Yansheng Du | Human beta-amyloid antibody and use thereof for treatment of alzheimer's disease |
US20030092145A1 (en) * | 2000-08-24 | 2003-05-15 | Vic Jira | Viral vaccine composition, process, and methods of use |
ATE441663T1 (de) * | 2000-09-06 | 2009-09-15 | Aventis Pharma Sa | Verfahren und zusammensetzungen für amyloidosis- verbundene krankheiten |
IT1319277B1 (it) | 2000-10-24 | 2003-09-26 | Chiesi Farma Spa | Proteine di fusione utili per il trattamento di immunizzazione dellamalattia di alzheimer. |
IL139308A0 (en) | 2000-10-26 | 2001-11-25 | Marikovsky Moshe | Peptides from amyloid precursor protein which inhibit tumor growth and metastasis |
DE60128138T2 (de) * | 2000-11-02 | 2008-01-03 | Cornell Research Foundation, Inc. | In vivo multiphoton diagnostische detektion und bilddarstellung einer neurodegenerativen erkrankung |
JP2004534511A (ja) | 2000-11-27 | 2004-11-18 | プラエシス ファーマシューティカルズ インク. | アミロイド形成性疾患を治療するための治療薬及びその使用法 |
US7700751B2 (en) | 2000-12-06 | 2010-04-20 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize β-amyloid peptide |
TWI255272B (en) * | 2000-12-06 | 2006-05-21 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
AU2002246734A1 (en) | 2000-12-27 | 2002-08-12 | University Of Texas Health Science Center Houston | Prion isomers, methods of making, methods of using, and compositions and products comprising prion isomers |
WO2002059621A2 (en) | 2001-01-24 | 2002-08-01 | Bayer Corporation | Regulation of transthyretin to treat obesity |
EP1251138B1 (en) | 2001-04-19 | 2006-07-26 | Hermann Dr. Schätzl | Prion protein dimers useful for vaccination |
WO2002088306A2 (en) * | 2001-04-30 | 2002-11-07 | Eli Lilly And Company | Humanized antibodies |
DE60229051D1 (de) * | 2001-04-30 | 2008-11-06 | Lilly Co Eli | Humanisierte antikörper |
US6906169B2 (en) * | 2001-05-25 | 2005-06-14 | United Biomedical, Inc. | Immunogenic peptide composition comprising measles virus Fprotein Thelper cell epitope (MUFThl-16) and N-terminus of β-amyloid peptide |
GB0113179D0 (en) | 2001-05-31 | 2001-07-25 | Novartis Ag | Organic compounds |
WO2003000714A2 (en) | 2001-06-22 | 2003-01-03 | Panacea Pharmaceuticals, Inc. | Compositions and methods for preventing protein aggregation in neurodegenerative diseases |
JP4317010B2 (ja) | 2001-07-25 | 2009-08-19 | ピーディーエル バイオファーマ,インコーポレイティド | IgG抗体の安定な凍結乾燥医薬製剤 |
US20030135035A1 (en) | 2001-08-09 | 2003-07-17 | Mark Shannon | Human ZZAP1 protein |
JP2005500389A (ja) | 2001-08-17 | 2005-01-06 | イーライ・リリー・アンド・カンパニー | Aβに関連する病態および疾患を治療するための、可溶性Aβに高い親和性を有する抗体の使用 |
US20060073149A1 (en) | 2001-08-17 | 2006-04-06 | Bales Kelly R | Rapid improvement of cognition in condition related to abeta |
CA2451998A1 (en) | 2001-08-17 | 2003-02-27 | Eli Lilly And Company | Anti-a.beta. antibodies |
US20030082191A1 (en) | 2001-08-29 | 2003-05-01 | Poduslo Joseph F. | Treatment for central nervous system disorders |
US6907297B2 (en) | 2001-09-28 | 2005-06-14 | Ethicon, Inc. | Expandable intracardiac return electrode and method of use |
US7781413B2 (en) | 2001-10-31 | 2010-08-24 | Board Of Regents, The University Of Texas System | SEMA3B inhibits tumor growth and induces apoptosis in cancer cells |
DK1441589T3 (da) | 2001-11-08 | 2012-08-06 | Abbott Biotherapeutics Corp | Stabil, flydende, farmaceutisk sammensætning af IgG-antistoffer |
EP1572894B1 (en) | 2001-11-21 | 2016-04-13 | New York University | Synthetic immunogenic but non-deposit-forming polypeptides and peptides homologous to amyloid beta, prion protein, amylin, alpha synuclein, or polyglutamine repeats for induction of an immune response thereto |
US20050227941A1 (en) | 2001-12-17 | 2005-10-13 | Karen Duff | Sequestration of ass in the periphery in the absence of immunomodulating agent as a therapeutic approach for the treatment or prevention of beta-amyloid related diseases |
AR038568A1 (es) | 2002-02-20 | 2005-01-19 | Hoffmann La Roche | Anticuerpos anti-a beta y su uso |
DE60334364D1 (de) | 2002-02-21 | 2010-11-11 | Univ California | Behandlungsverfahren unter verwendung von anti-cd22-antikörpern |
MY139983A (en) * | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
US7132100B2 (en) | 2002-06-14 | 2006-11-07 | Medimmune, Inc. | Stabilized liquid anti-RSV antibody formulations |
DE60336902D1 (de) | 2002-07-19 | 2011-06-09 | Cytos Biotechnology Ag | Impfstoffzusammensetzungen enthaltende amyloid beta 1-6 antigenarrays |
WO2004013172A2 (en) | 2002-07-24 | 2004-02-12 | Innogenetics N.V. | Fragments of beta-amyloid as targets for vaccination against alzheimer disease |
AU2003279728B2 (en) | 2002-10-01 | 2007-09-27 | Northwestern University | Amyloid beta-derived diffusible ligands (addls), addl-surrogates, addl-binding molecules, and uses thereof |
US20060019850A1 (en) | 2002-10-31 | 2006-01-26 | Korzenski Michael B | Removal of particle contamination on a patterned silicon/silicon dioxide using dense fluid/chemical formulations |
FR2846667B1 (fr) | 2002-11-06 | 2004-12-31 | Pasteur Institut | Fragments variables d'anticorps de camelides a chaine unique diriges contre le peptide beta-amyloide 1-42 et leurs applications pour le diagnostic et le traitement des maladies neuroagregatives |
US20040191243A1 (en) | 2002-12-13 | 2004-09-30 | Bei Chen | System and method for stabilizing antibodies with histidine |
US6787129B1 (en) | 2003-01-13 | 2004-09-07 | Zenitech Llc | Castor polyester as gloss agents in anionic systems |
KR20050118669A (ko) | 2003-02-01 | 2005-12-19 | 뉴랄랩 리미티드 | 가용성 a-베타에 대한 항체를 생성하기 위한 능동 면역화 |
WO2004071408A2 (en) | 2003-02-10 | 2004-08-26 | Applied Molecular Evolution, Inc. | Aβ BINDING MOLECULES |
PT1610820E (pt) | 2003-04-04 | 2010-12-16 | Novartis Ag | Formulações de elevada concentração de anticorpos e proteínas |
EP1480041A1 (en) | 2003-05-22 | 2004-11-24 | Innogenetics N.V. | Method for the prediction, diagnosis and differential diagnosis of Alzheimer's disease |
TWI306458B (en) | 2003-05-30 | 2009-02-21 | Elan Pharma Int Ltd | Humanized antibodies that recognize beta amyloid peptide |
US20060182321A1 (en) | 2003-07-07 | 2006-08-17 | Agency For Science, Technology And Research | Method and apparatus for extracting third ventricle information |
WO2005014041A2 (en) | 2003-07-24 | 2005-02-17 | Novartis Ag | Use of an amyloid beta dna vaccine for the treatment and/or prevention of amyloid diseases |
WO2005026211A2 (en) | 2003-09-05 | 2005-03-24 | Eli Lilly And Company | Anti-ghrelin antibodies |
CA2445743A1 (en) | 2003-10-08 | 2005-04-08 | The University Of British Columbia | Methods for modulating neuronal responses |
SG149013A1 (en) | 2003-12-17 | 2009-01-29 | Wyeth Corp | Immunogenic peptide carrier conjugates and methods of producing same |
EP2479184A3 (en) | 2003-12-17 | 2013-09-04 | Janssen Alzheimer Immunotherapy | Beta immunogenic peptide carrier conjugates and methods of producing the same |
US20050214222A1 (en) | 2004-02-13 | 2005-09-29 | Mckinnon Stuart J | In vivo imaging of amyloid plaques in glaucoma using intravenous injectable dyes |
DK1771208T3 (da) | 2004-07-02 | 2013-09-02 | Univ Pittsburgh | Anvendelse af thioflavin radiomarkerede derivater i amyloid billeddannelse til vurdering af anti-amyloide terapier |
EA016357B1 (ru) * | 2004-07-30 | 2012-04-30 | Ринат Ньюросайенс Корп. | Антитела, направленные против бета-амилоидного пептида, и способы их применения |
WO2006042158A2 (en) * | 2004-10-05 | 2006-04-20 | Wyeth | Methods and compositions for improving recombinant protein production |
US20060160161A1 (en) | 2004-10-26 | 2006-07-20 | Elan Pharmaceuticals, Inc. | Methods for assessing antibodies to neurodegenerative disease-associated antigens |
AR051800A1 (es) | 2004-12-15 | 2007-02-07 | Wyeth Corp | Anticuerpos a beta usados en mejorar la cognicion |
WO2006066089A1 (en) | 2004-12-15 | 2006-06-22 | Neuralab Limited | Humanized amyloid beta antibodies for use in improving cognition |
WO2006066118A2 (en) | 2004-12-15 | 2006-06-22 | Neuralab Limited | Contextual fear test for predicting efficacy of alzheimer immunotherapeutic treatment |
TW200636066A (en) | 2004-12-15 | 2006-10-16 | Elan Pharm Inc | Humanized antibodies that recognize beta amyloid peptide |
US20060240486A1 (en) | 2004-12-15 | 2006-10-26 | Johnson-Wood Kelly L | Immunoprecipitation-based assay for predicting in vivo efficacy of beta-amyloid antibodies |
GT200600031A (es) | 2005-01-28 | 2006-08-29 | Formulacion anticuerpo anti a beta | |
KR20070107079A (ko) | 2005-01-28 | 2007-11-06 | 와이어쓰 | 안정화된 액체 폴리펩타이드 제형 |
EP2388274A1 (en) | 2005-06-17 | 2011-11-23 | Janssen Alzheimer Immunotherapy | Methods of purifying anti A Beta antibodies |
AU2006270084B2 (en) | 2005-07-18 | 2011-08-25 | Merck Sharp & Dohme Corp. | Spiropiperidine beta-secretase inhibitors for the treatment of Alzheimer's disease |
CN101558080A (zh) * | 2005-11-10 | 2009-10-14 | 罗斯坎普研究有限责任公司 | Aβ肽片段对血管生成的调节 |
WO2010044803A1 (en) | 2008-10-17 | 2010-04-22 | Elan Pharma International Limited | Treatment of amyloidogenic diseases |
JP2010521651A (ja) | 2007-03-12 | 2010-06-24 | 独立行政法人放射線医学総合研究所 | 脳内のアミロイド関連神経炎症の画像化 |
US8003097B2 (en) | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
KR20100016661A (ko) | 2007-04-18 | 2010-02-12 | 얀센 알츠하이머 이뮤노테라피 | 대뇌 아밀로이드 혈관병증의 예방 및 치료 |
EP2182983B1 (en) | 2007-07-27 | 2014-05-21 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases with humanised anti-abeta antibodies |
JO3076B1 (ar) | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | نظم العلاج المناعي المعتمد على حالة apoe |
KR20160135843A (ko) | 2008-09-18 | 2016-11-28 | 세다르스-신나이 메디칼 센터 | 알츠하이머병의 검출을 위한 광학적 방법 |
-
2003
- 2003-03-11 MY MYPI20030834A patent/MY139983A/en unknown
- 2003-03-12 UY UY27721A patent/UY27721A1/es not_active Application Discontinuation
- 2003-03-12 NZ NZ535769A patent/NZ535769A/en not_active IP Right Cessation
- 2003-03-12 ES ES03711559T patent/ES2389541T3/es not_active Expired - Lifetime
- 2003-03-12 EA EA200401170A patent/EA010902B1/ru not_active IP Right Cessation
- 2003-03-12 BR BRPI0308143-5A patent/BR0308143A/pt not_active IP Right Cessation
- 2003-03-12 PE PE2003000251A patent/PE20040207A1/es not_active Application Discontinuation
- 2003-03-12 AU AU2003214152A patent/AU2003214152B2/en not_active Ceased
- 2003-03-12 WO PCT/US2003/007715 patent/WO2003077858A2/en active Search and Examination
- 2003-03-12 MX MXPA04008740A patent/MXPA04008740A/es active IP Right Grant
- 2003-03-12 JP JP2003575912A patent/JP2006503549A/ja active Pending
- 2003-03-12 CN CN038058162A patent/CN1703426B/zh not_active Expired - Fee Related
- 2003-03-12 ZA ZA200406616A patent/ZA200406616B/en unknown
- 2003-03-12 SG SG2006077101A patent/SG180018A1/en unknown
- 2003-03-12 KR KR1020117003856A patent/KR20110027846A/ko not_active Application Discontinuation
- 2003-03-12 TW TW092105368A patent/TWI328116B/zh not_active IP Right Cessation
- 2003-03-12 KR KR1020047014176A patent/KR101122871B1/ko not_active IP Right Cessation
- 2003-03-12 PL PL375159A patent/PL215258B1/pl unknown
- 2003-03-12 GE GEAP8440A patent/GEP20084474B/en unknown
- 2003-03-12 EP EP03711559A patent/EP1554311B1/en not_active Expired - Lifetime
- 2003-03-12 CA CA2478049A patent/CA2478049C/en not_active Expired - Fee Related
- 2003-03-12 US US10/388,214 patent/US7256273B2/en not_active Expired - Fee Related
- 2003-03-12 AR ARP030100863A patent/AR038953A1/es not_active Application Discontinuation
- 2003-03-12 IL IL16362603A patent/IL163626A0/xx unknown
- 2003-12-03 UA UA20041008271A patent/UA89469C2/uk unknown
-
2004
- 2004-08-19 IL IL163626A patent/IL163626A/en not_active IP Right Cessation
- 2004-09-21 EC EC2004005314A patent/ECSP045314A/es unknown
- 2004-09-23 NO NO20043992A patent/NO20043992L/no unknown
- 2004-10-11 IS IS7499A patent/IS7499A/is unknown
- 2004-10-12 CO CO04101910A patent/CO5611164A2/es active IP Right Grant
- 2004-10-12 HR HR20040950A patent/HRP20040950A2/hr not_active Application Discontinuation
-
2006
- 2006-05-03 HK HK06105249.2A patent/HK1085222A1/xx not_active IP Right Cessation
-
2007
- 2007-08-13 US US11/893,123 patent/US8128928B2/en not_active Expired - Fee Related
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105348387A (zh) * | 2010-08-14 | 2016-02-24 | Abbvie公司 | β淀粉样蛋白结合蛋白 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1703426A (zh) | 识别β-淀粉样肽的人源化抗体 | |
CN1798766A (zh) | 识别β-淀粉样肽的人源化抗体 | |
TWI803523B (zh) | Tigit抗體、其抗原結合片段及醫藥用途 | |
CN1541225A (zh) | 识别β淀粉样肽的人源化抗体 | |
CN104822389B (zh) | 识别α-突触核蛋白的抗体 | |
KR101340699B1 (ko) | 인간 모노클로날 항체 인간 cd134(ox40) 및이의 제조 및 사용 방법 | |
KR101197839B1 (ko) | Apoe 상태에 의존적인 면역치료 요법 | |
US8519112B2 (en) | Humanized antibodies against monocyte chemotactic proteins | |
CN1426423A (zh) | 螯合淀粉样蛋白β肽的人源化抗体 | |
CN1993143A (zh) | 用于治疗多发性硬化的方法 | |
JP2008524247A (ja) | 認知の改善における使用のためのアミロイドβ抗体 | |
CN1359301A (zh) | 致淀粉样病的预防和治疗 | |
JP2008523815A (ja) | 認知の改善における使用のためのヒト化アミロイドβ抗体 | |
CN1278736A (zh) | 抗人gp39的人源化抗体、包含所述人源化抗体的组合物及其治疗用途 | |
TWI791006B (zh) | 包含bdnf之融合蛋白質 | |
CN1383450A (zh) | 对人肿瘤坏死因子α具有特异性的抗体分子及其用途 | |
CN1662558A (zh) | 人cd22特异性抗体及其治疗和诊断应用 | |
CN1473854A (zh) | 用于治疗il4介导疾病的重组il4抗体 | |
TW201843179A (zh) | 用於治療或預防認知障礙之人類化抗體、用於製備其之方法及用於使用其來治療或預防認知障礙之藥劑 | |
CN101052417A (zh) | 突触核蛋白病以及淀粉样变性病的预防和治疗 | |
CN1078250C (zh) | 抗免疫球蛋白等模式标本的重整形单克隆抗体 | |
CN101031588A (zh) | 药物组合物,融合物和结合物 | |
CN1842541A (zh) | 调节nk细胞活性的组合物和方法 | |
CN1207127A (zh) | 抗人gp39的人源化抗体,含有该抗体的组合物及其治疗用途 | |
JP2012233002A (ja) | 認知の改善における使用のためのアミロイドβ抗体 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1085222 Country of ref document: HK |
|
ASS | Succession or assignment of patent right |
Owner name: ISLAND OF THE INTERNATIONAL PHARMACEUTICAL CO.; A Free format text: FORMER OWNER: NEURALAB LTD.; APPLICANT Effective date: 20080222 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20080222 Address after: Irish West Applicant after: Neuralab Ltd. Co-applicant after: WYETH Address before: Bermuda Smith Applicant before: Neuro Lab Co.,Ltd. Co-applicant before: WYETH |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C56 | Change in the name or address of the patentee | ||
CP01 | Change in the name or title of a patent holder |
Address after: Irish West Co-patentee after: WYETH LLC Patentee after: Neuralab Ltd. Address before: Irish West Co-patentee before: WYETH Patentee before: Neuralab Ltd. |
|
C56 | Change in the name or address of the patentee | ||
CP03 | Change of name, title or address |
Address after: Irish West Co-patentee after: WYETH LLC Patentee after: Neuralab Ltd. Address before: Irish West Co-patentee before: Wyeth LLC Patentee before: Neuralab Ltd. |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1085222 Country of ref document: HK |
|
ASS | Succession or assignment of patent right |
Owner name: KELI MAGUA CO., LTD. Free format text: FORMER OWNER: ELAN PHARMA INT LTD. Effective date: 20111212 |
|
C41 | Transfer of patent application or patent right or utility model | ||
C56 | Change in the name or address of the patentee |
Owner name: JANSSEN ALZHEIMER IMMUNOTHERAPY CO. Free format text: FORMER NAME: KELI MAGUA CO., LTD. |
|
CP01 | Change in the name or title of a patent holder |
Address after: Dublin, Ireland Co-patentee after: WYETH LLC Patentee after: JANSSEN ALZHEIMER IMMUNOTHERAPY Address before: Dublin, Ireland Co-patentee before: Wyeth LLC Patentee before: Kelima melon Co.,Ltd. |
|
TR01 | Transfer of patent right |
Effective date of registration: 20111212 Address after: Dublin, Ireland Co-patentee after: WYETH LLC Patentee after: Kelima melon Co.,Ltd. Address before: Irish West Co-patentee before: Wyeth LLC Patentee before: Neuralab Ltd. |
|
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20100428 Termination date: 20180312 |
|
CF01 | Termination of patent right due to non-payment of annual fee |