CA2756801A1 - Tissue kallikrein for the treatment of pancreatic .beta.-cell dysfunction - Google Patents
Tissue kallikrein for the treatment of pancreatic .beta.-cell dysfunction Download PDFInfo
- Publication number
- CA2756801A1 CA2756801A1 CA2756801A CA2756801A CA2756801A1 CA 2756801 A1 CA2756801 A1 CA 2756801A1 CA 2756801 A CA2756801 A CA 2756801A CA 2756801 A CA2756801 A CA 2756801A CA 2756801 A1 CA2756801 A1 CA 2756801A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- purified
- isolated
- beta
- klk1
- 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
- 230000004064 dysfunction Effects 0.000 title claims abstract description 21
- 101710176219 Kallikrein-1 Proteins 0.000 title abstract description 10
- 102000057032 Tissue Kallikreins Human genes 0.000 title abstract description 5
- 238000000034 method Methods 0.000 claims abstract description 36
- 210000004153 islets of langerhan Anatomy 0.000 claims abstract description 25
- 239000012634 fragment Substances 0.000 claims abstract description 19
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 43
- 102100038297 Kallikrein-1 Human genes 0.000 claims description 42
- 101000605522 Homo sapiens Kallikrein-1 Proteins 0.000 claims description 36
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 36
- 229920001184 polypeptide Polymers 0.000 claims description 33
- 230000000694 effects Effects 0.000 claims description 21
- 210000004027 cell Anatomy 0.000 claims description 20
- 150000001413 amino acids Chemical group 0.000 claims description 18
- 102000012479 Serine Proteases Human genes 0.000 claims description 13
- 108010022999 Serine Proteases Proteins 0.000 claims description 13
- 108010003195 Kallidin Proteins 0.000 claims description 12
- FYSKZKQBTVLYEQ-FSLKYBNLSA-N Kallidin Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)CCC1 FYSKZKQBTVLYEQ-FSLKYBNLSA-N 0.000 claims description 12
- 238000002560 therapeutic procedure Methods 0.000 claims description 10
- 210000000056 organ Anatomy 0.000 claims description 7
- 210000000130 stem cell Anatomy 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 230000035755 proliferation Effects 0.000 claims description 4
- 230000008929 regeneration Effects 0.000 claims description 3
- 238000011069 regeneration method Methods 0.000 claims description 3
- 230000001771 impaired effect Effects 0.000 claims description 2
- 108010058188 Low-Molecular-Weight Kininogen Proteins 0.000 claims 10
- 230000002159 abnormal effect Effects 0.000 claims 2
- 230000006320 pegylation Effects 0.000 claims 2
- 238000002360 preparation method Methods 0.000 claims 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
- 229940125396 insulin Drugs 0.000 description 21
- 201000010099 disease Diseases 0.000 description 20
- 102000004877 Insulin Human genes 0.000 description 18
- 108090001061 Insulin Proteins 0.000 description 18
- 125000003275 alpha amino acid group Chemical group 0.000 description 16
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 16
- 229940024606 amino acid Drugs 0.000 description 15
- 235000001014 amino acid Nutrition 0.000 description 14
- 108091028043 Nucleic acid sequence Proteins 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 13
- 150000007523 nucleic acids Chemical group 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- 241000282414 Homo sapiens Species 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 210000000496 pancreas Anatomy 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 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 8
- 206010012601 diabetes mellitus Diseases 0.000 description 8
- 239000008103 glucose Substances 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 102000001399 Kallikrein Human genes 0.000 description 7
- 108060005987 Kallikrein Proteins 0.000 description 7
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 241001494479 Pecora Species 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 210000004457 myocytus nodalis Anatomy 0.000 description 3
- 210000004923 pancreatic tissue Anatomy 0.000 description 3
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 3
- 229960001052 streptozocin Drugs 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
- 206010003694 Atrophy Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 2
- 241000282567 Macaca fascicularis Species 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 102000003827 Plasma Kallikrein Human genes 0.000 description 2
- 108090000113 Plasma Kallikrein Proteins 0.000 description 2
- 101000605527 Rattus norvegicus Kallikrein-1 Proteins 0.000 description 2
- 108700022175 Tissue Kallikreins Proteins 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 230000037444 atrophy Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 101150087654 chrnd gene Proteins 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 230000000762 glandular Effects 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229940039088 kininogenase Drugs 0.000 description 2
- 210000000663 muscle cell Anatomy 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)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](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 description 1
- YPMOAQISONSSNL-UHFFFAOYSA-N 8-hydroxyoctyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCCCCCCO YPMOAQISONSSNL-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 238000012756 BrdU staining Methods 0.000 description 1
- 108010075254 C-Peptide Proteins 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 235000019005 Digitaria californica Nutrition 0.000 description 1
- 241001115843 Digitaria californica Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101100510281 Homo sapiens KL gene Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 102000010631 Kininogens Human genes 0.000 description 1
- 108010077861 Kininogens Proteins 0.000 description 1
- 108010093008 Kinins Proteins 0.000 description 1
- 102000002397 Kinins Human genes 0.000 description 1
- 241000272168 Laridae Species 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 101000605526 Mus musculus Kallikrein-1 Proteins 0.000 description 1
- 101100180428 Mus musculus Klk1b1 gene Proteins 0.000 description 1
- 208000016222 Pancreatic disease Diseases 0.000 description 1
- 241000282515 Papio hamadryas Species 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 101100453992 Rattus norvegicus Ngfg gene Proteins 0.000 description 1
- 241000288960 Saguinus oedipus Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- WLDHEUZGFKACJH-UHFFFAOYSA-K amaranth Chemical compound [Na+].[Na+].[Na+].C12=CC=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(O)=C1N=NC1=CC=C(S([O-])(=O)=O)C2=CC=CC=C12 WLDHEUZGFKACJH-UHFFFAOYSA-K 0.000 description 1
- -1 amino acid analogies Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000004993 emission spectroscopy Methods 0.000 description 1
- 210000003890 endocrine cell Anatomy 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 230000009229 glucose formation Effects 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 235000021233 hypercaloric diet Nutrition 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 238000013227 male C57BL/6J mice Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000007410 oral glucose tolerance test Methods 0.000 description 1
- 208000024691 pancreas disease Diseases 0.000 description 1
- 210000000277 pancreatic duct Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000003186 pharmaceutical solution Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 235000008729 phenylalanine Nutrition 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000000276 sedentary effect Effects 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression 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
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4853—Kallikrein (3.4.21.34 or 3.4.21.35)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Emergency Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16317309P | 2009-03-25 | 2009-03-25 | |
| US61/163,173 | 2009-03-25 | ||
| PCT/CA2010/000413 WO2010108262A1 (en) | 2009-03-25 | 2010-03-25 | TISSUE KALLIKREIN FOR THE TREATMENT OF PANCREATIC β-CELL DYSFUNCTION |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2756801A1 true CA2756801A1 (en) | 2010-09-30 |
Family
ID=42780097
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2756801A Abandoned CA2756801A1 (en) | 2009-03-25 | 2010-03-25 | Tissue kallikrein for the treatment of pancreatic .beta.-cell dysfunction |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20120070425A1 (enExample) |
| EP (1) | EP2411042A4 (enExample) |
| JP (1) | JP2012521366A (enExample) |
| CN (1) | CN102438648A (enExample) |
| AU (1) | AU2010228068A1 (enExample) |
| CA (1) | CA2756801A1 (enExample) |
| NZ (1) | NZ595364A (enExample) |
| WO (1) | WO2010108262A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12329805B2 (en) | 2017-03-09 | 2025-06-17 | Diamedica Inc. | Dosage forms of tissue kallikrein 1 |
| EP4435099A4 (en) * | 2021-11-16 | 2025-08-06 | Zonhon Biopharma Inst Inc | UNDERGLYCOSYLATED KALLIKREIN I, ITS MODIFIER POLYETHYLENE GLYCOL AND ITS PHARMACEUTICAL USE |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ582930A (en) | 2007-07-20 | 2012-11-30 | Diamedica Inc | Tissue kallikrein for the treatment of diseases associated with amyloid protein |
| EP2720703A4 (en) * | 2011-06-17 | 2015-07-22 | Univ Johns Hopkins | METHOD FOR INCREASING INSULIN SENSITIVITY AND TREATING DIABETES |
| US20130315891A1 (en) | 2012-05-25 | 2013-11-28 | Matthew Charles | Formulations of human tissue kallikrein-1 for parenteral delivery and related methods |
| US20130323222A1 (en) | 2012-06-04 | 2013-12-05 | Matthew Charles | Human tissue kallikrein 1 glycosylation isoforms |
| CN104073482A (zh) * | 2013-12-30 | 2014-10-01 | 江苏众红生物工程创药研究院有限公司 | 聚乙二醇化的组织激肽释放酶及其制备方法和应用 |
| CN112481268B (zh) * | 2021-01-25 | 2024-01-30 | 河南大学 | 一种棉花启动子PGhPGF及其重组载体和应用 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5534615A (en) | 1994-04-25 | 1996-07-09 | Genentech, Inc. | Cardiac hypertrophy factor and uses therefor |
| CA2327541A1 (en) * | 1998-05-22 | 1999-12-02 | Entremed, Inc. | Compositions and methods for inhibiting endothelial cell proliferation and regulating angiogenesis using serine proteases |
| CN1228447C (zh) * | 2001-02-20 | 2005-11-23 | 深圳市人民医院 | 一种含有人胰腺组织激肽释放酶成熟蛋白基因的重组表达载体 |
| CN100338212C (zh) * | 2003-01-29 | 2007-09-19 | 中国科学院大连化学物理研究所 | 人组织激肽释放酶的微囊化细胞及其微囊化方法和应用 |
| CN101094869A (zh) * | 2004-08-03 | 2007-12-26 | 戴埃克斯有限公司 | Hk1结合蛋白 |
| JP2008515774A (ja) * | 2004-08-03 | 2008-05-15 | ダイアックス コーポレイション | ｈＫ１結合タンパク質 |
| WO2008011713A1 (en) * | 2006-07-26 | 2008-01-31 | Diamedica Inc. | Methods of diagnosis and treatment for metabolic disorders |
| WO2008016883A2 (en) * | 2006-07-31 | 2008-02-07 | Activesite Pharmaceuticals, Inc. | Inhibitors of plasma kallikrein |
| CN101134953B (zh) * | 2007-07-02 | 2011-02-09 | 广东天普生化医药股份有限公司 | 重组人胰激肽原酶 |
| CN101255438B (zh) * | 2008-04-11 | 2012-01-25 | 深圳大学 | 表达人组织激肽释放酶的转基因莱茵衣藻的构建方法 |
-
2010
- 2010-03-25 EP EP10755352A patent/EP2411042A4/en not_active Ceased
- 2010-03-25 CA CA2756801A patent/CA2756801A1/en not_active Abandoned
- 2010-03-25 JP JP2012501089A patent/JP2012521366A/ja active Pending
- 2010-03-25 AU AU2010228068A patent/AU2010228068A1/en not_active Abandoned
- 2010-03-25 NZ NZ595364A patent/NZ595364A/xx not_active IP Right Cessation
- 2010-03-25 WO PCT/CA2010/000413 patent/WO2010108262A1/en not_active Ceased
- 2010-03-25 CN CN2010800181825A patent/CN102438648A/zh active Pending
-
2011
- 2011-09-23 US US13/241,882 patent/US20120070425A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12329805B2 (en) | 2017-03-09 | 2025-06-17 | Diamedica Inc. | Dosage forms of tissue kallikrein 1 |
| EP4435099A4 (en) * | 2021-11-16 | 2025-08-06 | Zonhon Biopharma Inst Inc | UNDERGLYCOSYLATED KALLIKREIN I, ITS MODIFIER POLYETHYLENE GLYCOL AND ITS PHARMACEUTICAL USE |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2411042A4 (en) | 2012-12-12 |
| NZ595364A (en) | 2013-09-27 |
| EP2411042A1 (en) | 2012-02-01 |
| CN102438648A (zh) | 2012-05-02 |
| JP2012521366A (ja) | 2012-09-13 |
| AU2010228068A1 (en) | 2011-10-20 |
| WO2010108262A1 (en) | 2010-09-30 |
| US20120070425A1 (en) | 2012-03-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2756801A1 (en) | Tissue kallikrein for the treatment of pancreatic .beta.-cell dysfunction | |
| Zatorski et al. | Role of glucagon-like peptides in inflammatory bowel diseases—current knowledge and future perspectives | |
| PL187917B1 (pl) | Oczyszczony lub izolowany polipeptyd, kompozycja farmaceutyczna, zastosowanie skutecznej ilości aktywnego fragmentu prosapozyny, zastosowanie skutecznej ilości polipeptydu, peptyd i jego zastosowanie | |
| Rühl et al. | Functional expression of the peptide transporter PEPT2 in the mammalian enteric nervous system | |
| EP2229952B1 (en) | Plasma anti-diabetic NUCB2 peptide (pladin and nesfatin-1n) and uses thereof | |
| CN102389413A (zh) | 用于治疗糖尿病的组合物及其应用 | |
| MX2008015657A (es) | Polipeptidos de factor de crecimiento similares a insulina estabilizados. | |
| CN104039357A (zh) | 胰腺β-细胞增殖的调节 | |
| TW201729833A (zh) | 用於治療澱粉樣沈著症之方法及組合物 | |
| Lagler | Current and emerging therapies for mucopolysaccharidoses | |
| US6274549B1 (en) | Treatment of type 1 diabetes | |
| EP2985034A1 (en) | Treating neoplasms with neurotoxin | |
| KR20070116587A (ko) | 유착 관절낭염을 치료하는 방법 | |
| WO2023122355A2 (en) | Methods of treating or preventing infusion-related reactions | |
| Shaikh et al. | Advanced approaches in insulin delivery | |
| KR20130122927A (ko) | Ｄｋｋ2 단백질 또는 그 유전자를 포함하는 발기부전 예방 또는 치료용 조성물 및 그의 용도 | |
| US9839671B2 (en) | Peptide and uses therefor | |
| CN112165955A (zh) | 抑制骨癌引起的异常性疼痛 | |
| US8945575B2 (en) | Treatment of IgE-mediated disease | |
| US20130090289A1 (en) | Method of Treatment of Type 2 Diabetes | |
| CN119979502B (zh) | 一种防治tau疾病的多肽及其应用 | |
| US20200046700A1 (en) | Focal adhesion kinase inhibitor as a therapeutic agent in diabetes | |
| Wang et al. | Codelivery of NGFR100W and VEGFA mRNA Enhances Vascular and Neural Repair in Diabetic Peripheral Neuropathy | |
| Liu et al. | Dust mites and mugwort allergens disrupt the nasal mucosal epithelial barrier by inhibiting mitochondrial biogenesis | |
| Woelfle | Linking the teneurin-Latrophilin interaction with glucose metabolism: role of the teneurin C-terminal associated peptide (TCAP)-1 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20160329 |