CA2819679A1 - Compositions and methods for treating amyloid plaque associated symptoms - Google Patents
Compositions and methods for treating amyloid plaque associated symptoms Download PDFInfo
- Publication number
- CA2819679A1 CA2819679A1 CA2819679A CA2819679A CA2819679A1 CA 2819679 A1 CA2819679 A1 CA 2819679A1 CA 2819679 A CA2819679 A CA 2819679A CA 2819679 A CA2819679 A CA 2819679A CA 2819679 A1 CA2819679 A1 CA 2819679A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- antibody
- amino acid
- apoe
- acid sequence
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 44
- 208000024891 symptom Diseases 0.000 title claims abstract description 28
- 208000037259 Amyloid Plaque Diseases 0.000 title claims abstract description 22
- 239000000203 mixture Substances 0.000 title abstract description 26
- 230000003247 decreasing effect Effects 0.000 claims abstract description 14
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 160
- 238000006467 substitution reaction Methods 0.000 claims description 49
- 210000004408 hybridoma Anatomy 0.000 claims description 27
- 150000007523 nucleic acids Chemical group 0.000 claims description 22
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 20
- 208000024827 Alzheimer disease Diseases 0.000 claims description 16
- 210000003169 central nervous system Anatomy 0.000 claims description 10
- 210000004556 brain Anatomy 0.000 claims description 8
- 230000006870 function Effects 0.000 claims description 7
- 230000001771 impaired effect Effects 0.000 claims description 6
- 230000001965 increasing effect Effects 0.000 claims description 6
- 206010010904 Convulsion Diseases 0.000 claims description 5
- 108091026890 Coding region Proteins 0.000 claims description 4
- 230000006399 behavior Effects 0.000 claims description 4
- 230000003920 cognitive function Effects 0.000 claims description 4
- 210000001320 hippocampus Anatomy 0.000 claims description 4
- 238000011161 development Methods 0.000 claims description 3
- 230000010483 emotional dysregulation Effects 0.000 claims description 3
- 210000000653 nervous system Anatomy 0.000 claims description 3
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 2
- 230000002159 abnormal effect Effects 0.000 claims description 2
- 102000013918 Apolipoproteins E Human genes 0.000 claims 6
- 108010025628 Apolipoproteins E Proteins 0.000 claims 6
- 230000009885 systemic effect Effects 0.000 claims 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims 1
- 241000282414 Homo sapiens Species 0.000 abstract description 44
- 101710095339 Apolipoprotein E Proteins 0.000 description 27
- 102100029470 Apolipoprotein E Human genes 0.000 description 27
- 101710117290 Aldo-keto reductase family 1 member C4 Proteins 0.000 description 17
- 241000699670 Mus sp. Species 0.000 description 17
- 101150037123 APOE gene Proteins 0.000 description 16
- 101100216294 Danio rerio apoeb gene Proteins 0.000 description 16
- 108060003951 Immunoglobulin Proteins 0.000 description 16
- 102000018358 immunoglobulin Human genes 0.000 description 16
- 108090000765 processed proteins & peptides Proteins 0.000 description 14
- 238000011282 treatment Methods 0.000 description 13
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 9
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 9
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 9
- 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 description 9
- 238000009472 formulation Methods 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 231100000331 toxic Toxicity 0.000 description 8
- 230000002588 toxic effect Effects 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 108010060159 Apolipoprotein E4 Proteins 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 210000000349 chromosome Anatomy 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 4
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 4
- 230000006735 deficit Effects 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000006724 microglial activation Effects 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- 101100096579 Drosophila melanogaster sqd gene Proteins 0.000 description 2
- 208000007542 Paresis Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 210000001642 activated microglia Anatomy 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 210000004602 germ cell Anatomy 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000007914 intraventricular administration Methods 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000007505 plaque formation Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000007790 solid phase Substances 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
- 239000000758 substrate Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 206010054196 Affect lability Diseases 0.000 description 1
- 238000010173 Alzheimer-disease mouse model Methods 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 102000001049 Amyloid Human genes 0.000 description 1
- 108010094108 Amyloid Proteins 0.000 description 1
- 108010032595 Antibody Binding Sites Proteins 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010002942 Apathy Diseases 0.000 description 1
- 108010060219 Apolipoprotein E2 Proteins 0.000 description 1
- 108010060215 Apolipoprotein E3 Proteins 0.000 description 1
- 102000008128 Apolipoprotein E3 Human genes 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 206010058504 Ballismus Diseases 0.000 description 1
- 206010069632 Bladder dysfunction Diseases 0.000 description 1
- 208000008720 Bone Marrow Neoplasms Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 208000033001 Complex partial seizures Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 1
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 1
- 208000014540 Functional gastrointestinal disease Diseases 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 1
- 101000771674 Homo sapiens Apolipoprotein E Proteins 0.000 description 1
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 206010027925 Monoparesis Diseases 0.000 description 1
- 101100055876 Mus musculus Apoe gene Proteins 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- XOJVVFBFDXDTEG-UHFFFAOYSA-N Norphytane Natural products CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 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
- 102000003992 Peroxidases Human genes 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 206010058895 Psychogenic seizure Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 206010040030 Sensory loss Diseases 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 201000006491 bone marrow cancer Diseases 0.000 description 1
- 201000007637 bowel dysfunction Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- WLNARFZDISHUGS-MIXBDBMTSA-N cholesteryl hemisuccinate Chemical compound C1C=C2C[C@@H](OC(=O)CCC(O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 WLNARFZDISHUGS-MIXBDBMTSA-N 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 229940028334 follicle stimulating hormone Drugs 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 230000001339 gustatory effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 206010019465 hemiparesis Diseases 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 102000053020 human ApoE Human genes 0.000 description 1
- 102000054751 human RUNX1T1 Human genes 0.000 description 1
- 208000003906 hydrocephalus Diseases 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- -1 phosphatidyl glycerols Chemical class 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 230000007470 synaptic degeneration Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 125000003698 tetramethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000001755 vocal effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
-
- 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
-
- 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Neurology (AREA)
- Wood Science & Technology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- General Engineering & Computer Science (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41906010P | 2010-12-02 | 2010-12-02 | |
| US61/419,060 | 2010-12-02 | ||
| US201161548542P | 2011-10-18 | 2011-10-18 | |
| US61/548,542 | 2011-10-18 | ||
| PCT/US2011/063121 WO2012075422A2 (en) | 2010-12-02 | 2011-12-02 | Compositions and methods for treating amyloid plaque associated symptoms |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2819679A1 true CA2819679A1 (en) | 2012-06-07 |
Family
ID=46172597
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2819679A Abandoned CA2819679A1 (en) | 2010-12-02 | 2011-12-02 | Compositions and methods for treating amyloid plaque associated symptoms |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US20140037638A1 (enExample) |
| EP (1) | EP2646053A4 (enExample) |
| JP (1) | JP2014502276A (enExample) |
| KR (1) | KR20140017513A (enExample) |
| CN (1) | CN103338786A (enExample) |
| AU (1) | AU2011336360A1 (enExample) |
| BR (1) | BR112013013723A2 (enExample) |
| CA (1) | CA2819679A1 (enExample) |
| MX (1) | MX2013006116A (enExample) |
| NZ (1) | NZ611614A (enExample) |
| RU (1) | RU2013130002A (enExample) |
| SG (1) | SG190952A1 (enExample) |
| WO (1) | WO2012075422A2 (enExample) |
| ZA (1) | ZA201303996B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013168174A1 (en) * | 2012-05-08 | 2013-11-14 | Ramot At Tel-Aviv University Ltd. | Apoe4 antibodies for treatment of neurodegenerative conditions |
| BR112017006419A2 (pt) | 2014-09-30 | 2017-12-19 | Univ Washington | medições cinéticas de tau |
| EP3452074A4 (en) * | 2016-05-03 | 2019-12-11 | University of South Florida | COMPOSITIONS AND METHOD FOR MODULATING THE ABETA PROTEIN |
| US11124562B2 (en) | 2016-10-28 | 2021-09-21 | Washington University | Anti-ApoE antibodies |
| CA3070100A1 (en) * | 2017-07-17 | 2019-01-24 | Janssen Biotech, Inc. | Antigen binding regions against fibronectin type iii domains and methods of using the same |
| CN120098122A (zh) * | 2019-05-28 | 2025-06-06 | 总医院公司 | Apoe抗体、融合蛋白及其用途 |
| WO2023069892A1 (en) * | 2021-10-19 | 2023-04-27 | Short Jay M | Conditionally active proteins for neurodegenerative diseases |
| AU2023399623A1 (en) * | 2022-11-30 | 2025-07-03 | Bio-Techne Corporation | Natural killer cell engagers |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI951701L (fi) * | 1992-10-13 | 1995-04-10 | Univ Duke | Menetelmät Alzheimerin taudin tunnistamiseksi |
| AR047729A1 (es) * | 2003-11-28 | 2006-02-15 | Astrazeneca Ab | Anticuerpos terapeuticos que se unen a la apolipoproteina e (apoe) |
| AU2005228764A1 (en) * | 2004-03-30 | 2005-10-13 | Renomedix Institute Inc. | Remedy for prion disease and method of producing the same |
| EP1991252A2 (en) * | 2006-02-21 | 2008-11-19 | Oklahoma Medical Research Foundation | Treatment of alzheimer's disease with inhibitors of apoe binding to apoe receptor |
| AU2007332473B2 (en) * | 2006-12-14 | 2012-09-27 | Forerunner Pharma Research Co., Ltd. | Anti-Claudin-3 monoclonal antibody, and treatment and diagnosis of cancer using the same |
| CL2008002775A1 (es) * | 2007-09-17 | 2008-11-07 | Amgen Inc | Uso de un agente de unión a esclerostina para inhibir la resorción ósea. |
| US9102717B2 (en) * | 2010-03-01 | 2015-08-11 | The J. David Gladstone Institutes | Antibody specific for apolipoprotein and methods of use thereof |
-
2011
- 2011-12-02 RU RU2013130002/10A patent/RU2013130002A/ru not_active Application Discontinuation
- 2011-12-02 NZ NZ611614A patent/NZ611614A/en not_active IP Right Cessation
- 2011-12-02 CA CA2819679A patent/CA2819679A1/en not_active Abandoned
- 2011-12-02 MX MX2013006116A patent/MX2013006116A/es not_active Application Discontinuation
- 2011-12-02 US US13/990,777 patent/US20140037638A1/en not_active Abandoned
- 2011-12-02 BR BR112013013723A patent/BR112013013723A2/pt not_active IP Right Cessation
- 2011-12-02 JP JP2013542218A patent/JP2014502276A/ja active Pending
- 2011-12-02 WO PCT/US2011/063121 patent/WO2012075422A2/en not_active Ceased
- 2011-12-02 AU AU2011336360A patent/AU2011336360A1/en not_active Abandoned
- 2011-12-02 EP EP11844128.6A patent/EP2646053A4/en not_active Withdrawn
- 2011-12-02 SG SG2013042288A patent/SG190952A1/en unknown
- 2011-12-02 CN CN2011800667946A patent/CN103338786A/zh active Pending
- 2011-12-02 KR KR1020137016719A patent/KR20140017513A/ko not_active Withdrawn
-
2013
- 2013-05-31 ZA ZA2013/03996A patent/ZA201303996B/en unknown
-
2016
- 2016-08-22 US US15/243,495 patent/US20160355581A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20160355581A1 (en) | 2016-12-08 |
| US20140037638A1 (en) | 2014-02-06 |
| CN103338786A (zh) | 2013-10-02 |
| WO2012075422A2 (en) | 2012-06-07 |
| JP2014502276A (ja) | 2014-01-30 |
| WO2012075422A3 (en) | 2012-10-04 |
| ZA201303996B (en) | 2015-10-28 |
| EP2646053A4 (en) | 2014-05-28 |
| NZ611614A (en) | 2015-07-31 |
| KR20140017513A (ko) | 2014-02-11 |
| EP2646053A2 (en) | 2013-10-09 |
| SG190952A1 (en) | 2013-07-31 |
| MX2013006116A (es) | 2013-10-17 |
| BR112013013723A2 (pt) | 2019-09-24 |
| RU2013130002A (ru) | 2015-01-10 |
| AU2011336360A1 (en) | 2013-07-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20160355581A1 (en) | Compositions and methods for treating amyloid plaque associated symptoms | |
| TWI705975B (zh) | 抗－N3pGlu類澱粉β肽抗體及其用途 | |
| AU2006319358B2 (en) | Anti-Abeta 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 | |
| CN1426423B (zh) | 螯合淀粉样蛋白β肽的人源化抗体 | |
| JP6955721B2 (ja) | ＲＧＭａ結合タンパク質及びその使用 | |
| US20230416393A1 (en) | Cd6 antibody for treatment of t-cell mediated diseases or disorders | |
| US8741298B2 (en) | APOE immunotherapy | |
| US7122374B1 (en) | Amyloid beta-protein 3(pE)-42 antibodies and uses thereof | |
| US20100322932A1 (en) | Methods for amyloid removal using anti-amyloid antibodies | |
| CN112166121B (zh) | 神经生长因子的单克隆抗体及其编码基因和应用 | |
| TW201441256A (zh) | 抗β類澱粉蛋白單株抗體 | |
| KR20010052374A (ko) | 항-아밀로이드 항체를 이용한 아밀로이드 제거 방법들 | |
| CN105431203A (zh) | 治疗性融合蛋白 | |
| JP2019514994A (ja) | 脊髄性筋萎縮症を治療するための組成物及び方法 | |
| CA3030872A1 (en) | Compositions and methods for treating frontotemporal dementia | |
| AU2023200728A1 (en) | Prevention or treatment method for peripheral neuropathy or pain accompanying disease in which peripheral neuropathy or astrocyte disorder is recognized | |
| CN115175932B (zh) | 用于治疗阿尔茨海默病的中和抗β淀粉样蛋白抗体 | |
| WO2025119350A1 (zh) | 靶向Tau的特异性结合蛋白及其应用 | |
| JP2024506409A (ja) | 抗体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20171204 |