CA2997958A1 - Pcsk9 antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device - Google Patents
Pcsk9 antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device Download PDFInfo
- Publication number
- CA2997958A1 CA2997958A1 CA2997958A CA2997958A CA2997958A1 CA 2997958 A1 CA2997958 A1 CA 2997958A1 CA 2997958 A CA2997958 A CA 2997958A CA 2997958 A CA2997958 A CA 2997958A CA 2997958 A1 CA2997958 A1 CA 2997958A1
- Authority
- CA
- Canada
- Prior art keywords
- antibody
- preparation
- patient
- intestinal wall
- tissue penetrating
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 153
- 210000001035 gastrointestinal tract Anatomy 0.000 title abstract description 99
- 238000012377 drug delivery Methods 0.000 title description 48
- 101150094724 PCSK9 gene Proteins 0.000 title 1
- 239000002775 capsule Substances 0.000 claims abstract description 195
- 230000000968 intestinal effect Effects 0.000 claims abstract description 159
- 238000000034 method Methods 0.000 claims abstract description 135
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 26
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 claims abstract description 11
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 claims abstract description 9
- 230000000149 penetrating effect Effects 0.000 claims description 228
- 210000000813 small intestine Anatomy 0.000 claims description 143
- 239000000463 material Substances 0.000 claims description 94
- 108010028554 LDL Cholesterol Proteins 0.000 claims description 75
- 239000007787 solid Substances 0.000 claims description 52
- 229960004539 alirocumab Drugs 0.000 claims description 50
- 230000009467 reduction Effects 0.000 claims description 45
- 210000004369 blood Anatomy 0.000 claims description 31
- 239000008280 blood Substances 0.000 claims description 31
- 238000003780 insertion Methods 0.000 claims description 27
- 230000037431 insertion Effects 0.000 claims description 27
- 238000002347 injection Methods 0.000 claims description 26
- 239000007924 injection Substances 0.000 claims description 26
- 229960002027 evolocumab Drugs 0.000 claims description 25
- 230000027455 binding Effects 0.000 claims description 24
- 238000009739 binding Methods 0.000 claims description 24
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 24
- 210000002966 serum Anatomy 0.000 claims description 24
- 230000002829 reductive effect Effects 0.000 claims description 23
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 22
- 229950011350 bococizumab Drugs 0.000 claims description 22
- 230000028993 immune response Effects 0.000 claims description 22
- 239000012530 fluid Substances 0.000 claims description 20
- 230000004044 response Effects 0.000 claims description 18
- 230000036470 plasma concentration Effects 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 14
- 230000037406 food intake Effects 0.000 claims description 14
- 230000001603 reducing effect Effects 0.000 claims description 14
- 230000000717 retained effect Effects 0.000 claims description 14
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 12
- 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 claims description 11
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 11
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 11
- 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 claims description 11
- 229960005370 atorvastatin Drugs 0.000 claims description 11
- 239000011230 binding agent Substances 0.000 claims description 10
- 239000008188 pellet Substances 0.000 claims description 10
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 10
- 238000010254 subcutaneous injection Methods 0.000 claims description 10
- 239000007929 subcutaneous injection Substances 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 230000003247 decreasing effect Effects 0.000 claims description 9
- 238000007918 intramuscular administration Methods 0.000 claims description 9
- 239000003638 chemical reducing agent Substances 0.000 claims description 7
- 239000007884 disintegrant Substances 0.000 claims description 7
- 238000010255 intramuscular injection Methods 0.000 claims description 7
- 239000007927 intramuscular injection Substances 0.000 claims description 7
- 210000000265 leukocyte Anatomy 0.000 claims description 7
- 230000007774 longterm Effects 0.000 claims description 7
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 6
- 238000012544 monitoring process Methods 0.000 claims description 6
- 238000012360 testing method Methods 0.000 claims description 6
- 230000002068 genetic effect Effects 0.000 claims description 5
- 230000014759 maintenance of location Effects 0.000 claims description 5
- 235000000346 sugar Nutrition 0.000 claims description 5
- 102000000704 Interleukin-7 Human genes 0.000 claims description 4
- 108010002586 Interleukin-7 Proteins 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 4
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 4
- 229940100994 interleukin-7 Drugs 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims description 3
- 238000004820 blood count Methods 0.000 claims description 3
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- 208000028867 ischemia Diseases 0.000 claims description 3
- 239000003755 preservative agent Substances 0.000 claims description 3
- 108020005544 Antisense RNA Proteins 0.000 claims description 2
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
- 239000003184 complementary RNA Substances 0.000 claims description 2
- PJRSUKFWFKUDTH-JWDJOUOUSA-N (2s)-6-amino-2-[[2-[[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]propanoyl]amino]acetyl]amino]propanoyl Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(N)=O PJRSUKFWFKUDTH-JWDJOUOUSA-N 0.000 claims 2
- 108010021753 peptide-Gly-Leu-amide Proteins 0.000 claims 2
- 208000031481 Pathologic Constriction Diseases 0.000 claims 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 claims 1
- 230000002335 preservative effect Effects 0.000 claims 1
- 208000037804 stenosis Diseases 0.000 claims 1
- 230000036262 stenosis Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 353
- 229940124597 therapeutic agent Drugs 0.000 abstract description 78
- 108090000623 proteins and genes Proteins 0.000 abstract description 51
- 102000004169 proteins and genes Human genes 0.000 abstract description 48
- 238000011282 treatment Methods 0.000 abstract description 22
- 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 abstract description 21
- 150000002632 lipids Chemical class 0.000 abstract description 11
- 235000012000 cholesterol Nutrition 0.000 abstract description 10
- 210000004303 peritoneum Anatomy 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 description 271
- 210000001519 tissue Anatomy 0.000 description 199
- 230000007246 mechanism Effects 0.000 description 91
- 239000007788 liquid Substances 0.000 description 50
- 239000000203 mixture Substances 0.000 description 47
- 230000015556 catabolic process Effects 0.000 description 45
- 238000006731 degradation reaction Methods 0.000 description 42
- 230000033001 locomotion Effects 0.000 description 36
- 239000000376 reactant Substances 0.000 description 30
- 238000000576 coating method Methods 0.000 description 26
- 239000000126 substance Substances 0.000 description 25
- 230000008602 contraction Effects 0.000 description 23
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- 230000002572 peristaltic effect Effects 0.000 description 21
- 229920000642 polymer Polymers 0.000 description 21
- 239000011248 coating agent Substances 0.000 description 19
- 210000000936 intestine Anatomy 0.000 description 18
- 239000007789 gas Substances 0.000 description 17
- 108010001831 LDL receptors Proteins 0.000 description 16
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 16
- 210000002784 stomach Anatomy 0.000 description 16
- 230000008901 benefit Effects 0.000 description 14
- 230000004071 biological effect Effects 0.000 description 14
- 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 14
- 208000032928 Dyslipidaemia Diseases 0.000 description 13
- 208000017170 Lipid metabolism disease Diseases 0.000 description 13
- 238000013459 approach Methods 0.000 description 13
- 210000002429 large intestine Anatomy 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 239000004698 Polyethylene Substances 0.000 description 12
- 239000000427 antigen Substances 0.000 description 12
- 102000036639 antigens Human genes 0.000 description 12
- 108091007433 antigens Proteins 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 239000012634 fragment Substances 0.000 description 12
- 238000002483 medication Methods 0.000 description 12
- -1 polyethylene Polymers 0.000 description 12
- 229920000573 polyethylene Polymers 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 102000023732 binding proteins Human genes 0.000 description 11
- 108091008324 binding proteins Proteins 0.000 description 11
- 230000009977 dual effect Effects 0.000 description 11
- 235000012054 meals Nutrition 0.000 description 11
- 206010020751 Hypersensitivity Diseases 0.000 description 10
- 238000006065 biodegradation reaction Methods 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 238000000926 separation method Methods 0.000 description 10
- 238000007920 subcutaneous administration Methods 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000002496 gastric effect Effects 0.000 description 9
- 230000003472 neutralizing effect Effects 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 108010007622 LDL Lipoproteins Proteins 0.000 description 8
- 102000007330 LDL Lipoproteins Human genes 0.000 description 8
- 108091005804 Peptidases Proteins 0.000 description 8
- 102000035195 Peptidases Human genes 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 8
- 230000009471 action Effects 0.000 description 8
- 208000030961 allergic reaction Diseases 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 230000002596 correlated effect Effects 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 230000035515 penetration Effects 0.000 description 8
- 239000002243 precursor Substances 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 102000004877 Insulin Human genes 0.000 description 7
- 108090001061 Insulin Proteins 0.000 description 7
- 239000004365 Protease Substances 0.000 description 7
- 230000002411 adverse Effects 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- 230000000712 assembly Effects 0.000 description 7
- 238000000429 assembly Methods 0.000 description 7
- 229920002988 biodegradable polymer Polymers 0.000 description 7
- 239000004621 biodegradable polymer Substances 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 229940125396 insulin Drugs 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 239000006187 pill Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 6
- 238000004132 cross linking Methods 0.000 description 6
- 239000000122 growth hormone Substances 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 238000000465 moulding Methods 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 231100001274 therapeutic index Toxicity 0.000 description 6
- 238000002604 ultrasonography Methods 0.000 description 6
- 206010067484 Adverse reaction Diseases 0.000 description 5
- 201000001320 Atherosclerosis Diseases 0.000 description 5
- 108010051696 Growth Hormone Proteins 0.000 description 5
- 102000018997 Growth Hormone Human genes 0.000 description 5
- 208000030673 Homozygous familial hypercholesterolemia Diseases 0.000 description 5
- 108060003951 Immunoglobulin Proteins 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 230000006838 adverse reaction Effects 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 238000007906 compression Methods 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- 239000002702 enteric coating Substances 0.000 description 5
- 238000009505 enteric coating Methods 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 230000005847 immunogenicity Effects 0.000 description 5
- 102000018358 immunoglobulin Human genes 0.000 description 5
- 238000005304 joining Methods 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 239000011736 potassium bicarbonate Substances 0.000 description 5
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 5
- 235000015497 potassium bicarbonate Nutrition 0.000 description 5
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 5
- 206010002199 Anaphylactic shock Diseases 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 4
- 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 4
- 208000000112 Myalgia Diseases 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 239000000853 adhesive Substances 0.000 description 4
- 230000001070 adhesive effect Effects 0.000 description 4
- 208000003455 anaphylaxis Diseases 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 230000006835 compression Effects 0.000 description 4
- 238000002059 diagnostic imaging Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 230000009851 immunogenic response Effects 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- 210000001986 peyer's patch Anatomy 0.000 description 4
- 229960004540 secukinumab Drugs 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 230000009747 swallowing Effects 0.000 description 4
- 230000002792 vascular Effects 0.000 description 4
- 230000003442 weekly effect Effects 0.000 description 4
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 229920003134 Eudragit® polymer Polymers 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- 108010050904 Interferons Proteins 0.000 description 3
- 238000008214 LDL Cholesterol Methods 0.000 description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 238000004873 anchoring Methods 0.000 description 3
- 238000007664 blowing Methods 0.000 description 3
- 229960003735 brodalumab Drugs 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000004891 communication Methods 0.000 description 3
- 238000005056 compaction Methods 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000013583 drug formulation Substances 0.000 description 3
- 210000001198 duodenum Anatomy 0.000 description 3
- 238000002594 fluoroscopy Methods 0.000 description 3
- 102000053786 human PCSK9 Human genes 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 239000006072 paste Substances 0.000 description 3
- 238000010094 polymer processing Methods 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 238000007493 shaping process Methods 0.000 description 3
- 238000004088 simulation Methods 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- VPVXHAANQNHFSF-UHFFFAOYSA-N 1,4-dioxan-2-one Chemical compound O=C1COCCO1 VPVXHAANQNHFSF-UHFFFAOYSA-N 0.000 description 2
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 206010060933 Adverse event Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 2
- 108010011459 Exenatide Proteins 0.000 description 2
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=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](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)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(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 108010010234 HDL Lipoproteins Proteins 0.000 description 2
- 102000015779 HDL Lipoproteins Human genes 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 206010022095 Injection Site reaction Diseases 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 108090000445 Parathyroid hormone Proteins 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 108010022999 Serine Proteases Proteins 0.000 description 2
- 102000012479 Serine Proteases Human genes 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 210000000436 anus Anatomy 0.000 description 2
- 208000004670 arteriolosclerosis Diseases 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- 239000003833 bile salt Substances 0.000 description 2
- 229940093761 bile salts Drugs 0.000 description 2
- 229920000249 biocompatible polymer Polymers 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 238000000748 compression moulding Methods 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 238000001723 curing Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000002716 delivery method Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 229960001519 exenatide Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000019692 hotdogs Nutrition 0.000 description 2
- 210000003405 ileum Anatomy 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229940047124 interferons Drugs 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 210000001630 jejunum Anatomy 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 2
- 150000002605 large molecules Chemical class 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000000199 parathyroid hormone Substances 0.000 description 2
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000449 pharmaceutical disintegrant Substances 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229920006254 polymer film Polymers 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000001338 self-assembly Methods 0.000 description 2
- 238000000935 solvent evaporation Methods 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000000153 supplemental effect Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 description 2
- 238000007666 vacuum forming Methods 0.000 description 2
- DDYAPMZTJAYBOF-ZMYDTDHYSA-N (3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-4-amino-1-[[(2S,3S)-1-[[(1S)-1-carboxyethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoic acid Chemical class [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)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)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O DDYAPMZTJAYBOF-ZMYDTDHYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 108010067611 BMS-962476 Proteins 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000005853 Clathrin Human genes 0.000 description 1
- 108010019874 Clathrin Proteins 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 201000000057 Coronary Stenosis Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 206010014476 Elevated cholesterol Diseases 0.000 description 1
- 206010014486 Elevated triglycerides Diseases 0.000 description 1
- 206010053155 Epigastric discomfort Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
- 206010017788 Gastric haemorrhage Diseases 0.000 description 1
- 108010088406 Glucagon-Like Peptides Proteins 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](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(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
- NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 description 1
- 101150043052 Hamp gene Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 101710172072 Kexin Proteins 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](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(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 1
- 108010019598 Liraglutide Proteins 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 208000012266 Needlestick injury Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 102100036893 Parathyroid hormone Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 206010072563 Peripheral artery stenosis Diseases 0.000 description 1
- 206010034576 Peripheral ischaemia Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100040918 Pro-glucagon Human genes 0.000 description 1
- 101710180553 Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 206010057469 Vascular stenosis Diseases 0.000 description 1
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000573 anti-seizure effect Effects 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 229940125687 antiparasitic agent Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 229940049950 atorvastatin 10 mg Drugs 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 229940092738 beeswax Drugs 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000009286 beneficial effect 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
- 230000002902 bimodal effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000006800 cellular catabolic process Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229930193282 clathrin Natural products 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000002305 electric material Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 239000012943 hotmelt Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 230000001000 lipidemic effect Effects 0.000 description 1
- 229960002701 liraglutide Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 229920001684 low density polyethylene Polymers 0.000 description 1
- 239000004702 low-density polyethylene Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000006674 lysosomal degradation Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 238000002156 mixing Methods 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
- 210000004877 mucosa Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 229960005027 natalizumab Drugs 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 238000013105 post hoc analysis Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003611 pramlintide Drugs 0.000 description 1
- 108010029667 pramlintide Proteins 0.000 description 1
- NRKVKVQDUCJPIZ-MKAGXXMWSA-N pramlintide acetate Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NRKVKVQDUCJPIZ-MKAGXXMWSA-N 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 239000012781 shape memory material Substances 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000012899 standard injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 125000005591 trimellitate group Chemical group 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4891—Coated capsules; Multilayered drug free capsule shells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- 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
- A61K2039/541—Mucosal route
- A61K2039/542—Mucosal route oral/gastrointestinal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
- A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Vascular Medicine (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Mycology (AREA)
- Genetics & Genomics (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Anesthesiology (AREA)
- Cardiology (AREA)
- Microbiology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562215586P | 2015-09-08 | 2015-09-08 | |
| US62/215,586 | 2015-09-08 | ||
| US15/150,379 US11548940B2 (en) | 2014-05-15 | 2016-05-09 | Anti-interleukin antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
| US15/150,379 | 2016-05-09 | ||
| PCT/US2016/050832 WO2017044665A1 (en) | 2015-09-08 | 2016-09-08 | Pcsk9 antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2997958A1 true CA2997958A1 (en) | 2017-03-16 |
Family
ID=58240088
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2997958A Pending CA2997958A1 (en) | 2015-09-08 | 2016-09-08 | Pcsk9 antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP3347050B1 (enExample) |
| JP (3) | JP2018526403A (enExample) |
| CN (1) | CN108401419A (enExample) |
| AU (2) | AU2016320867B2 (enExample) |
| CA (1) | CA2997958A1 (enExample) |
| DK (1) | DK3347050T3 (enExample) |
| WO (1) | WO2017044665A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10689460B2 (en) | 2014-05-15 | 2020-06-23 | Incube Labs, Llc | PCSK9 antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
| CA2949236C (en) | 2014-05-15 | 2023-06-13 | Incube Labs, Llc | Pharmaceutical compositions and methods for fabrication of solid masses comprising polypeptides and/or proteins |
| KR102647155B1 (ko) | 2017-05-17 | 2024-03-15 | 메사추세츠 인스티튜트 오브 테크놀로지 | 자가-직립 물품 |
| US11541015B2 (en) | 2017-05-17 | 2023-01-03 | Massachusetts Institute Of Technology | Self-righting systems, methods, and related components |
| CA3100710A1 (en) | 2018-05-17 | 2019-11-21 | Massachusetts Institute Of Technology | Systems for electrical stimulation |
| US12128133B2 (en) | 2018-09-25 | 2024-10-29 | Rani Therapeutics, Llc | Ingestible device with expandable enclosure |
| CA3125348A1 (en) * | 2018-12-31 | 2020-07-09 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
| WO2020160399A1 (en) | 2019-02-01 | 2020-08-06 | Massachusetts Institute Of Technology | Systems and methods for liquid injection |
| CA3137539A1 (en) * | 2019-05-03 | 2020-10-20 | Rani Therapeutics, Llc | Clotting factor preparations for delivery into tissue of the intestinal tract using a swallowable drug delivery device |
| US11541216B2 (en) | 2019-11-21 | 2023-01-03 | Massachusetts Institute Of Technology | Methods for manufacturing tissue interfacing components |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8562589B2 (en) * | 2009-12-24 | 2013-10-22 | Rani Therapeutics, Llc | Swallowable drug delivery device and method of delivery |
| CN105999526B (zh) * | 2009-12-24 | 2019-07-05 | 拉尼医疗有限公司 | 可吞咽式药剂递送装置和药剂递送方法 |
| US9149617B2 (en) * | 2010-12-23 | 2015-10-06 | Rani Therapeutics, Llc | Device, system and methods for the oral delivery of therapeutic compounds |
| DK2726141T3 (da) * | 2011-06-29 | 2020-03-02 | Rani Therapeutics Llc | Enhed til oral levering af terapeutiske forbindelser |
| CA2840617C (en) * | 2011-06-29 | 2020-03-24 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
| JP2013023499A (ja) * | 2011-07-14 | 2013-02-04 | Pfizer Inc | 抗ｐｃｓｋ９抗体を用いた処置 |
| CA2939507A1 (en) * | 2014-02-14 | 2015-08-20 | Regeneron Pharmaceuticals, Inc. | Methods for treating patients with hypercholesterolemia that is not adequately controlled by moderate-dose statin therapy |
| CN107835682A (zh) * | 2015-05-08 | 2018-03-23 | 因库博实验室有限责任公司 | 使用可吞服药物递送装置递送至肠道内腔的抗白细胞介素抗体制剂 |
-
2016
- 2016-09-08 JP JP2018512407A patent/JP2018526403A/ja not_active Withdrawn
- 2016-09-08 EP EP16845073.2A patent/EP3347050B1/en active Active
- 2016-09-08 CA CA2997958A patent/CA2997958A1/en active Pending
- 2016-09-08 CN CN201680065019.1A patent/CN108401419A/zh active Pending
- 2016-09-08 DK DK16845073.2T patent/DK3347050T3/da active
- 2016-09-08 AU AU2016320867A patent/AU2016320867B2/en active Active
- 2016-09-08 WO PCT/US2016/050832 patent/WO2017044665A1/en not_active Ceased
-
2021
- 2021-07-30 JP JP2021125408A patent/JP2021169530A/ja active Pending
-
2023
- 2023-05-23 JP JP2023084891A patent/JP2023104992A/ja active Pending
- 2023-06-29 AU AU2023204153A patent/AU2023204153A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN108401419A (zh) | 2018-08-14 |
| AU2023204153A1 (en) | 2023-07-20 |
| EP3347050B1 (en) | 2025-01-15 |
| JP2018526403A (ja) | 2018-09-13 |
| EP3347050A4 (en) | 2019-05-22 |
| JP2021169530A (ja) | 2021-10-28 |
| WO2017044665A1 (en) | 2017-03-16 |
| DK3347050T3 (da) | 2025-04-14 |
| AU2016320867A1 (en) | 2018-04-05 |
| AU2016320867B2 (en) | 2023-03-30 |
| EP3347050A1 (en) | 2018-07-18 |
| JP2023104992A (ja) | 2023-07-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US12018090B2 (en) | PCSK9 antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device | |
| US20230174639A1 (en) | Anti-interleukin antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device | |
| EP3347050B1 (en) | Pcsk9 antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device | |
| US12201721B2 (en) | Clotting factor preparations for delivery into tissue of the intestinal tract using a swallowable drug delivery device | |
| US11814427B2 (en) | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device | |
| AU2021269453B2 (en) | Anti-interleukin antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device | |
| AU2012275112B2 (en) | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device | |
| US20150023962A1 (en) | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device | |
| US20230374155A1 (en) | Pcsk9 antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20210908 |
|
| EEER | Examination request |
Effective date: 20210908 |
|
| EEER | Examination request |
Effective date: 20210908 |
|
| EEER | Examination request |
Effective date: 20210908 |
|
| EEER | Examination request |
Effective date: 20210908 |
|
| EEER | Examination request |
Effective date: 20210908 |
|
| EEER | Examination request |
Effective date: 20210908 |