CA2952293A1 - Mic-1 fusion proteins and uses thereof - Google Patents

Mic-1 fusion proteins and uses thereof Download PDF

Info

Publication number: CA2952293A1
Authority: CA; Canada
Prior art keywords: seq; mic; compound according; serum albumin; protein
Prior art date: 2014-06-24
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 Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

CA2952293A

Other languages

English (en)

French (fr)

Inventor

Allan Christian Shaw

Charlotte HELGSTRAND

Michael Paolo Bastner SANDRINI

Sebastian Beck Jorgensen

Henning Thogersen

Kristian Sass-Orum

Sven Hastrup

Kim Vilbour Andersen

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Novo Nordisk AS

Original Assignee

Novo Nordisk AS

Priority date (The priority date 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 date listed.)

2014-06-24

Filing date

2015-06-17

Publication date

2015-12-30

2015-06-17 Application filed by Novo Nordisk AS filed Critical Novo Nordisk AS

2015-12-30 Publication of CA2952293A1 publication Critical patent/CA2952293A1/en

Status Withdrawn legal-status Critical Current

Links

102000037865 fusion proteins Human genes 0.000 title claims abstract description 149
108020001507 fusion proteins Proteins 0.000 title claims abstract description 149
102100026436 Regulator of MON1-CCZ1 complex Human genes 0.000 title 1
101710180672 Regulator of MON1-CCZ1 complex Proteins 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 250
102000008100 Human Serum Albumin Human genes 0.000 claims abstract description 172
108091006905 Human Serum Albumin Proteins 0.000 claims abstract description 172
108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 163
102100040896 Growth/differentiation factor 15 Human genes 0.000 claims abstract description 15
239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 9
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
101710194460 Growth/differentiation factor 15 Proteins 0.000 claims abstract 11
101000893549 Homo sapiens Growth/differentiation factor 15 Proteins 0.000 claims description 83
102000046181 human GDF15 Human genes 0.000 claims description 79
150000001413 amino acids Chemical class 0.000 claims description 69
230000037406 food intake Effects 0.000 claims description 48
235000012631 food intake Nutrition 0.000 claims description 48
125000003275 alpha amino acid group Chemical group 0.000 claims description 30
230000037396 body weight Effects 0.000 claims description 24
238000011282 treatment Methods 0.000 claims description 24
208000008589 Obesity Diseases 0.000 claims description 22
230000004927 fusion Effects 0.000 claims description 21
235000020824 obesity Nutrition 0.000 claims description 21
230000002265 prevention Effects 0.000 claims description 14
230000036528 appetite Effects 0.000 claims description 9
235000019789 appetite Nutrition 0.000 claims description 9
230000003247 decreasing effect Effects 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 7
230000001939 inductive effect Effects 0.000 claims description 7
208000030814 Eating disease Diseases 0.000 claims description 6
208000019454 Feeding and Eating disease Diseases 0.000 claims description 6
235000014632 disordered eating Nutrition 0.000 claims description 6
230000036186 satiety Effects 0.000 claims description 6
235000019627 satiety Nutrition 0.000 claims description 6
150000001408 amides Chemical class 0.000 claims description 5
150000003839 salts Chemical class 0.000 claims description 5
150000002148 esters Chemical class 0.000 claims description 4
239000000710 homodimer Substances 0.000 claims description 4
239000000556 agonist Substances 0.000 claims description 3
230000000694 effects Effects 0.000 abstract description 24
102000000597 Growth Differentiation Factor 15 Human genes 0.000 description 166
108010041834 Growth Differentiation Factor 15 Proteins 0.000 description 165
235000001014 amino acid Nutrition 0.000 description 74
229940024606 amino acid Drugs 0.000 description 72
108090000623 proteins and genes Proteins 0.000 description 54
102000004169 proteins and genes Human genes 0.000 description 49
235000018102 proteins Nutrition 0.000 description 46
210000004027 cell Anatomy 0.000 description 40
238000000034 method Methods 0.000 description 30
241000282414 Homo sapiens Species 0.000 description 29
230000014509 gene expression Effects 0.000 description 29
230000009467 reduction Effects 0.000 description 28
238000001890 transfection Methods 0.000 description 25
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 22
238000006467 substitution reaction Methods 0.000 description 21
238000000746 purification Methods 0.000 description 18
238000004113 cell culture Methods 0.000 description 15
108091028043 Nucleic acid sequence Proteins 0.000 description 14
238000001727 in vivo Methods 0.000 description 14
239000002609 medium Substances 0.000 description 14
210000002381 plasma Anatomy 0.000 description 14
239000013598 vector Substances 0.000 description 14
241001465754 Metazoa Species 0.000 description 13
230000004048 modification Effects 0.000 description 13
238000012986 modification Methods 0.000 description 13
241000700159 Rattus Species 0.000 description 12
230000000875 corresponding effect Effects 0.000 description 12
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
235000021316 daily nutritional intake Nutrition 0.000 description 11
239000000203 mixture Substances 0.000 description 11
125000000539 amino acid group Chemical class 0.000 description 10
239000013612 plasmid Substances 0.000 description 10
102000004196 processed proteins & peptides Human genes 0.000 description 10
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 10
108020004414 DNA Proteins 0.000 description 9
238000001597 immobilized metal affinity chromatography Methods 0.000 description 9
238000012453 sprague-dawley rat model Methods 0.000 description 9
108010076504 Protein Sorting Signals Proteins 0.000 description 8
239000003623 enhancer Substances 0.000 description 8
230000001225 therapeutic effect Effects 0.000 description 8
RUFHOVYUYSNDNY-ACZMJKKPSA-N Glu-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O RUFHOVYUYSNDNY-ACZMJKKPSA-N 0.000 description 7
239000012124 Opti-MEM Substances 0.000 description 7
206010033307 Overweight Diseases 0.000 description 7
230000002378 acidificating effect Effects 0.000 description 7
210000004369 blood Anatomy 0.000 description 7
239000008280 blood Substances 0.000 description 7
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
238000005516 engineering process Methods 0.000 description 7
239000013604 expression vector Substances 0.000 description 7
239000002953 phosphate buffered saline Substances 0.000 description 7
238000005119 centrifugation Methods 0.000 description 6
238000012217 deletion Methods 0.000 description 6
230000037430 deletion Effects 0.000 description 6
150000007523 nucleic acids Chemical class 0.000 description 6
229920001184 polypeptide Polymers 0.000 description 6
239000000126 substance Substances 0.000 description 6
102000009027 Albumins Human genes 0.000 description 5
108010088751 Albumins Proteins 0.000 description 5
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
235000011089 carbon dioxide Nutrition 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
230000003993 interaction Effects 0.000 description 5
238000004949 mass spectrometry Methods 0.000 description 5
238000003259 recombinant expression Methods 0.000 description 5
239000000523 sample Substances 0.000 description 5
238000001542 size-exclusion chromatography Methods 0.000 description 5
239000000243 solution Substances 0.000 description 5
239000006228 supernatant Substances 0.000 description 5
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
241000588724 Escherichia coli Species 0.000 description 4
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
239000013543 active substance Substances 0.000 description 4
238000007792 addition Methods 0.000 description 4
235000004279 alanine Nutrition 0.000 description 4
235000009582 asparagine Nutrition 0.000 description 4
229960001230 asparagine Drugs 0.000 description 4
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
238000001514 detection method Methods 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
235000013305 food Nutrition 0.000 description 4
239000000499 gel Substances 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
238000003780 insertion Methods 0.000 description 4
230000037431 insertion Effects 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
108010068617 neonatal Fc receptor Proteins 0.000 description 4
230000004044 response Effects 0.000 description 4
238000004007 reversed phase HPLC Methods 0.000 description 4
230000003248 secreting effect Effects 0.000 description 4
238000013518 transcription Methods 0.000 description 4
230000035897 transcription Effects 0.000 description 4
230000010474 transient expression Effects 0.000 description 4
102220635708 39S ribosomal protein L18, mitochondrial_C34A_mutation Human genes 0.000 description 3
102220635676 39S ribosomal protein L18, mitochondrial_H6D_mutation Human genes 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
KRXIWXCXOARFNT-ZLUOBGJFSA-N Asp-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O KRXIWXCXOARFNT-ZLUOBGJFSA-N 0.000 description 3
BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 3
239000007836 KH2PO4 Substances 0.000 description 3
101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 3
102100036407 Thioredoxin Human genes 0.000 description 3
238000010171 animal model Methods 0.000 description 3
-1 aromatic amino acids Chemical class 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000000872 buffer Substances 0.000 description 3
238000012512 characterization method Methods 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
235000005911 diet Nutrition 0.000 description 3
230000037213 diet Effects 0.000 description 3
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
229910000397 disodium phosphate Inorganic materials 0.000 description 3
235000019800 disodium phosphate Nutrition 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
238000001914 filtration Methods 0.000 description 3
238000007429 general method Methods 0.000 description 3
230000001976 improved effect Effects 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
210000003734 kidney Anatomy 0.000 description 3
238000013507 mapping Methods 0.000 description 3
239000000178 monomer Substances 0.000 description 3
229910000402 monopotassium phosphate Inorganic materials 0.000 description 3
235000019796 monopotassium phosphate Nutrition 0.000 description 3
108020004707 nucleic acids Proteins 0.000 description 3
102000039446 nucleic acids Human genes 0.000 description 3
230000037361 pathway Effects 0.000 description 3
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
229920000053 polysorbate 80 Polymers 0.000 description 3
229940068968 polysorbate 80 Drugs 0.000 description 3
230000004481 post-translational protein modification Effects 0.000 description 3
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
238000004064 recycling Methods 0.000 description 3
230000001105 regulatory effect Effects 0.000 description 3
230000010076 replication Effects 0.000 description 3
238000011160 research Methods 0.000 description 3
238000005063 solubilization Methods 0.000 description 3
230000007928 solubilization Effects 0.000 description 3
108060008226 thioredoxin Proteins 0.000 description 3
235000015961 tonic Nutrition 0.000 description 3
230000001256 tonic effect Effects 0.000 description 3
229960000716 tonics Drugs 0.000 description 3
YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 2
239000004475 Arginine Substances 0.000 description 2
KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 2
108700007698 Genetic Terminator Regions Proteins 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 2
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
125000003338 L-glutaminyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C(=O)N([H])[H] 0.000 description 2
241000699660 Mus musculus Species 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
108020004511 Recombinant DNA Proteins 0.000 description 2
240000004808 Saccharomyces cerevisiae Species 0.000 description 2
235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
238000000692 Student's t-test Methods 0.000 description 2
210000000577 adipose tissue Anatomy 0.000 description 2
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
239000007975 buffered saline Substances 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
238000002144 chemical decomposition reaction Methods 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
230000004087 circulation Effects 0.000 description 2
239000002299 complementary DNA Substances 0.000 description 2
229940125833 compound 23 Drugs 0.000 description 2
229940125961 compound 24 Drugs 0.000 description 2
230000001143 conditioned effect Effects 0.000 description 2
239000007857 degradation product Substances 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
238000010790 dilution Methods 0.000 description 2
210000001163 endosome Anatomy 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
238000009472 formulation Methods 0.000 description 2
239000012634 fragment Substances 0.000 description 2
230000002068 genetic effect Effects 0.000 description 2
239000008103 glucose Substances 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
235000009200 high fat diet Nutrition 0.000 description 2
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
230000002209 hydrophobic effect Effects 0.000 description 2
230000000977 initiatory effect Effects 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
238000004255 ion exchange chromatography Methods 0.000 description 2
YFVGRULMIQXYNE-UHFFFAOYSA-M lithium;dodecyl sulfate Chemical compound [Li+].CCCCCCCCCCCCOS([O-])(=O)=O YFVGRULMIQXYNE-UHFFFAOYSA-M 0.000 description 2
238000011068 loading method Methods 0.000 description 2
235000015263 low fat diet Nutrition 0.000 description 2
239000000463 material Substances 0.000 description 2
238000012544 monitoring process Methods 0.000 description 2
208000001022 morbid obesity Diseases 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
230000036470 plasma concentration Effects 0.000 description 2
108091033319 polynucleotide Proteins 0.000 description 2
102000040430 polynucleotide Human genes 0.000 description 2
239000002157 polynucleotide Substances 0.000 description 2
239000000047 product Substances 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
238000011084 recovery Methods 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
239000002904 solvent Substances 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
238000010186 staining Methods 0.000 description 2
125000003396 thiol group Chemical group [H]S* 0.000 description 2
238000011830 transgenic mouse model Methods 0.000 description 2
230000032258 transport Effects 0.000 description 2
210000003462 vein Anatomy 0.000 description 2
239000003643 water by type Substances 0.000 description 2
MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
101150026173 ARG2 gene Proteins 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
241000024188 Andala Species 0.000 description 1
102000004506 Blood Proteins Human genes 0.000 description 1
108010017384 Blood Proteins Proteins 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
238000001712 DNA sequencing Methods 0.000 description 1
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
208000032928 Dyslipidaemia Diseases 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
238000002965 ELISA Methods 0.000 description 1
241000233866 Fungi Species 0.000 description 1
241000238631 Hexapoda Species 0.000 description 1
101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
102000003839 Human Proteins Human genes 0.000 description 1
108090000144 Human Proteins Proteins 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
108010002350 Interleukin-2 Proteins 0.000 description 1
101710151321 Melanostatin Proteins 0.000 description 1
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
102400000064 Neuropeptide Y Human genes 0.000 description 1
238000010220 Pearson correlation analysis Methods 0.000 description 1
241000233805 Phoenix Species 0.000 description 1
229920001213 Polysorbate 20 Polymers 0.000 description 1
108010069820 Pro-Opiomelanocortin Proteins 0.000 description 1
239000000683 Pro-Opiomelanocortin Substances 0.000 description 1
102100027467 Pro-opiomelanocortin Human genes 0.000 description 1
241000700157 Rattus norvegicus Species 0.000 description 1
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
239000012505 Superdex™ Substances 0.000 description 1
101710167003 Thiol:disulfide interchange protein DsbC Proteins 0.000 description 1
102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
230000009471 action Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
238000001042 affinity chromatography Methods 0.000 description 1
239000008272 agar Substances 0.000 description 1
238000013019 agitation Methods 0.000 description 1
230000004075 alteration Effects 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
239000000883 anti-obesity agent Substances 0.000 description 1
229940125710 antiobesity agent Drugs 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
238000003556 assay Methods 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
230000008901 benefit Effects 0.000 description 1
239000012148 binding buffer Substances 0.000 description 1
230000007321 biological mechanism Effects 0.000 description 1
OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
239000008366 buffered solution Substances 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
230000024245 cell differentiation Effects 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000009956 central mechanism Effects 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000002759 chromosomal effect Effects 0.000 description 1
210000000349 chromosome Anatomy 0.000 description 1
238000011284 combination treatment Methods 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
229940125773 compound 10 Drugs 0.000 description 1
229940126142 compound 16 Drugs 0.000 description 1
229940125846 compound 25 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
208000012696 congenital leptin deficiency Diseases 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
238000012258 culturing Methods 0.000 description 1
235000018417 cysteine Nutrition 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
210000000172 cytosol Anatomy 0.000 description 1
238000007405 data analysis Methods 0.000 description 1
230000006240 deamidation Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
230000029087 digestion Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000000539 dimer Substances 0.000 description 1
238000006471 dimerization reaction Methods 0.000 description 1
201000010099 disease Diseases 0.000 description 1
238000009826 distribution Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000002158 endotoxin Substances 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
210000003527 eukaryotic cell Anatomy 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
239000006277 exogenous ligand Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
238000010353 genetic engineering Methods 0.000 description 1
102000034238 globular proteins Human genes 0.000 description 1
108091005896 globular proteins Proteins 0.000 description 1
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
230000012010 growth Effects 0.000 description 1
239000005556 hormone Substances 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
102000056982 human CD33 Human genes 0.000 description 1
230000005661 hydrophobic surface Effects 0.000 description 1
201000001421 hyperglycemia Diseases 0.000 description 1
230000002267 hypothalamic effect Effects 0.000 description 1
230000002163 immunogen Effects 0.000 description 1
230000005847 immunogenicity Effects 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000011534 incubation Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
238000005304 joining Methods 0.000 description 1
238000013493 large scale plasmid preparation Methods 0.000 description 1
238000011031 large-scale manufacturing process Methods 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
229920006008 lipopolysaccharide Polymers 0.000 description 1
239000007788 liquid Substances 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
229910021645 metal ion Inorganic materials 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
230000035772 mutation Effects 0.000 description 1
AEMBWNDIEFEPTH-UHFFFAOYSA-N n-tert-butyl-n-ethylnitrous amide Chemical compound CCN(N=O)C(C)(C)C AEMBWNDIEFEPTH-UHFFFAOYSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
230000000414 obstructive effect Effects 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
239000008188 pellet Substances 0.000 description 1
239000000813 peptide hormone Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
239000004033 plastic Substances 0.000 description 1
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
210000004896 polypeptide structure Anatomy 0.000 description 1
229940068977 polysorbate 20 Drugs 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000002243 precursor Substances 0.000 description 1
230000008569 process Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
208000023958 prostate neoplasm Diseases 0.000 description 1
230000004845 protein aggregation Effects 0.000 description 1
239000012460 protein solution Substances 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
230000003362 replicative effect Effects 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
239000012723 sample buffer Substances 0.000 description 1
238000013341 scale-up Methods 0.000 description 1
238000012216 screening Methods 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 1
201000002859 sleep apnea Diseases 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
235000011008 sodium phosphates Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000004114 suspension culture Methods 0.000 description 1
238000004885 tandem mass spectrometry Methods 0.000 description 1
238000012360 testing method Methods 0.000 description 1
ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)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](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)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](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
230000000930 thermomechanical effect Effects 0.000 description 1
JADVWWSKYZXRGX-UHFFFAOYSA-M thioflavine T Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C1=[N+](C)C2=CC=C(C)C=C2S1 JADVWWSKYZXRGX-UHFFFAOYSA-M 0.000 description 1
229940094937 thioredoxin Drugs 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000002103 transcriptional effect Effects 0.000 description 1
239000012096 transfection reagent Substances 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
238000003146 transient transfection Methods 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
230000006433 tumor necrosis factor production Effects 0.000 description 1
208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
210000003556 vascular endothelial cell Anatomy 0.000 description 1
238000012795 verification Methods 0.000 description 1
238000011179 visual inspection Methods 0.000 description 1
239000011800 void material Substances 0.000 description 1
239000011534 wash buffer Substances 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
230000037221 weight management Effects 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/38—Albumins
- A61K38/385—Serum albumin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- 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
- A61P3/04—Anorexiants; Antiobesity agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/76—Albumins
- C07K14/765—Serum albumin, e.g. HSA
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Proteomics, Peptides & Aminoacids (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Organic Chemistry (AREA)
Gastroenterology & Hepatology (AREA)
Zoology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Molecular Biology (AREA)
Epidemiology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Immunology (AREA)
Toxicology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Obesity (AREA)
Hematology (AREA)
Diabetes (AREA)
Child & Adolescent Psychology (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)

CA2952293A 2014-06-24 2015-06-17 Mic-1 fusion proteins and uses thereof Withdrawn CA2952293A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP14173664		2014-06-24
EP14173664.5		2014-06-24
PCT/EP2015/063596 WO2015197446A1 (en)	2014-06-24	2015-06-17	Mic-1 fusion proteins and uses thereof

Publications (1)

Publication Number	Publication Date
CA2952293A1 true CA2952293A1 (en)	2015-12-30

Family

ID=51032955

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2952293A Withdrawn CA2952293A1 (en)	2014-06-24	2015-06-17	Mic-1 fusion proteins and uses thereof

Country Status (15)

Country	Link
US (2)	US9272019B2 (2)
EP (1)	EP3160496B1 (2)
JP (1)	JP6696915B2 (2)
KR (1)	KR20170020383A (2)
CN (1)	CN106459222A (2)
AR (1)	AR100945A1 (2)
AU (1)	AU2015279525A1 (2)
BR (1)	BR112016029848A2 (2)
CA (1)	CA2952293A1 (2)
IL (1)	IL249327A0 (2)
MX (1)	MX2016016063A (2)
RU (1)	RU2017101436A (2)
TW (1)	TW201613958A (2)
WO (1)	WO2015197446A1 (2)
ZA (1)	ZA201608214B (2)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP2694092B1 (en)	2011-04-08	2017-01-04	Amgen Inc.	Method of treating or ameliorating metabolic disorders using growth differentiation factor 15 (gdf-15)
US9862752B2 (en)	2013-07-31	2018-01-09	Amgen Inc.	Growth differentiation factor 15 (GDF-15) constructs
US10588980B2 (en)	2014-06-23	2020-03-17	Novartis Ag	Fatty acids and their use in conjugation to biomolecules
JP6946304B2 (ja)	2015-12-22	2021-10-06	ノバルティスアーゲー	増殖分化因子１５（ｇｄｆ−１５）を使用して代謝障害を処置するまたは軽快させる方法
US10336812B2 (en) *	2016-05-10	2019-07-02	Janssen Biotech, Inc.	GDF15 fusion proteins and uses thereof
KR102433503B1 (ko) *	2016-05-24	2022-08-18	노보 노르디스크 에이/에스	Mic-1 화합물 및 이것의 사용
GB201615844D0 (en) *	2016-09-16	2016-11-02	Genagon Therapeutics Ab	Agents for use in therapy
US20200069774A1 (en) *	2016-12-06	2020-03-05	St Vincent's Hospital Sydney Limited	Treatment of obesity and eating disorders
GB201700567D0 (en)	2017-01-12	2017-03-01	Genagon Therapeutics Ab	Therapeutic agents
GB201700553D0 (en) *	2017-01-12	2017-03-01	Genagon Therapeutics Ab	Therapeutic agents
JP2020517657A (ja)	2017-04-20	2020-06-18	ノヴォノルディスクアー／エス	アルブミン融合タンパク質の精製方法
TWI710377B (zh)	2017-05-23	2020-11-21	丹麥商諾佛儂迪克股份有限公司	Ｍｉｃ－１化合物及其用途
CN111163795A (zh)	2017-09-10	2020-05-15	诺沃挪第克公司	用于治疗肥胖症的mic-1和glp-1
US11913039B2 (en)	2018-03-30	2024-02-27	Alexion Pharmaceuticals, Inc.	Method for producing recombinant alkaline phosphatase
TWI724392B (zh)	2018-04-06	2021-04-11	美商美國禮來大藥廠	生長分化因子15促效劑化合物及其使用方法
CR20200510A (es)	2018-04-09	2020-11-26	Amgen Inc	Protreínas de fusión del factor de diferenciación de crecimiento 15
EP3833974A2 (en)	2018-08-10	2021-06-16	Novartis AG	Gfral extracellular domains and methods of use
US12268733B2 (en)	2018-08-10	2025-04-08	Alexion Pharmaceuticals, Inc.	Methods of treating neurofibromatosis type 1 and related conditions with alkaline phosphatase
EA202191105A1 (ru)	2018-10-22	2021-08-03	Янссен Фармацевтика Нв	Слитые белки, полученные из глюкагоноподобного пептида 1 (glp1) и ростового фактора дифференцировки 15 (gdf15), и их применение
EP4041281B1 (en)	2019-10-04	2025-11-26	Amgen Inc.	Use of gdf15 for treating cardiometabolic syndrome and other conditions
CA3161302A1 (en) *	2019-11-26	2021-06-03	Yuhan Corporation	Long-acting gdf15 fusion protein and pharmaceutical composition comprising same
CA3161266A1 (en) *	2019-12-09	2021-06-17	Alexion Pharmaceuticals, Inc.	Alkaline phosphatase polypeptides and methods of use thereof
CA3159979A1 (en) *	2019-12-11	2021-06-17	Yeonchul Kim	Fusion polypeptide comprising gdf15 and polypeptide region capable of o-glycosylation
CN115379850A (zh) *	2019-12-24	2022-11-22	裘美娜治疗公司	再生性多肽及其用途
EP4085077A4 (en) *	2019-12-31	2024-01-17	Beijing QL Biopharmaceutical Co., Ltd.	Fusion proteins of glp-1 and gdf15 and conjugates thereof
WO2021194257A1 (ko) *	2020-03-25	2021-09-30	(주) 업테라	세포 투과성 펩티드 이량체, 이의 제조방법 및 이를 이용한 카고 전달 시스템
KR102195740B1 (ko) *	2020-03-25	2020-12-28	서울대학교산학협력단	세포 투과성 펩티드 이량체, 이의 제조방법 및 이를 이용한 카고 전달 시스템
AU2021337652B2 (en)	2020-09-04	2025-01-30	Alexion Pharmaceuticals, Inc.	Methods for treating bone mineralization disorders
EP4237438A4 (en)	2020-10-27	2024-11-27	Beijing QL Biopharmaceutical Co., Ltd.	GDF15 FUSION PROTEINS AND THEIR USE
CN112694520B (zh) *	2020-12-02	2023-01-17	图凌(杭州)生物医药有限公司	一种人工多肽hm、其抗体及在病理检测中的应用
BR112023016048A2 (pt)	2021-02-12	2023-11-14	Alexion Pharma Inc	Polipeptídeos de fosfatase alcalina e métodos de uso dos mesmos
WO2022219495A1 (en)	2021-04-12	2022-10-20	Novartis Ag	2-((4-((s)-2-(4-chloro-2-fluorophenyl)-2-methylbenzo[d][1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((s)-oxetan-2-yl)methyl)-1h-imidazole derivatives as activators of the glp1 receptor for the treatment of obesity
EP4476212A1 (en)	2022-02-10	2024-12-18	Novartis AG	2-((4-((s)-2-(4-chloro-2-fluorophenyl)-2-methylbenzo[d][1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((s)-oxetan-2-yl)methyl)-1h-imidazole derivatives as activators of the glp1 receptor for the treatment of obesity
EP4389762A1 (en)	2022-12-23	2024-06-26	Ospedale San Raffaele S.r.l.	Inhibitors of dux4 activity and their use in therapy.

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP2213743A1 (en)	2000-04-12	2010-08-04	Human Genome Sciences, Inc.	Albumin fusion proteins
CN1241946C (zh)	2002-07-01	2006-02-15	美国福源集团	对多种细胞具刺激增生作用的人血清白蛋白重组融合蛋白
EP2441466B1 (en)	2004-04-13	2014-07-23	St Vincent's Hospital Sydney Limited	MIC-1 inhibiting agent
EP2194064A1 (en) *	2004-05-13	2010-06-09	Eli Lilly & Company	FGF-21 fusion proteins
EP1771467A2 (en) *	2004-07-26	2007-04-11	Asterion Limited	Linkers
JP2010536341A (ja)	2007-08-15	2010-12-02	アムニクス，インコーポレイテッド	生物学的に活性なポリペプチドの特性を改変するための組成物および方法
EP3683228A3 (en) *	2012-01-26	2020-07-29	Amgen Inc.	Growth differentiation factor 15 (gdf-15) polypeptides
CA2862516C (en)	2012-03-27	2023-02-14	Ngm Biopharmaceuticals, Inc.	Compositions and methods of use for treating metabolic disorders
KR101993714B1 (ko)	2013-01-30	2019-06-28	엔지엠 바이오파마슈티컬스, 아이엔씨.	대사 장애를 치료하는데 이용하기 위한 조성물과 방법
US9862752B2 (en)	2013-07-31	2018-01-09	Amgen Inc.	Growth differentiation factor 15 (GDF-15) constructs

2015
- 2015-06-17 RU RU2017101436A patent/RU2017101436A/ru unknown
- 2015-06-17 MX MX2016016063A patent/MX2016016063A/es unknown
- 2015-06-17 EP EP15730140.9A patent/EP3160496B1/en not_active Withdrawn - After Issue
- 2015-06-17 CA CA2952293A patent/CA2952293A1/en not_active Withdrawn
- 2015-06-17 AU AU2015279525A patent/AU2015279525A1/en not_active Withdrawn
- 2015-06-17 TW TW104119532A patent/TW201613958A/zh unknown
- 2015-06-17 KR KR1020167037059A patent/KR20170020383A/ko not_active Withdrawn
- 2015-06-17 JP JP2016574944A patent/JP6696915B2/ja not_active Expired - Fee Related
- 2015-06-17 BR BR112016029848A patent/BR112016029848A2/pt not_active Application Discontinuation
- 2015-06-17 CN CN201580033507.XA patent/CN106459222A/zh not_active Withdrawn
- 2015-06-17 WO PCT/EP2015/063596 patent/WO2015197446A1/en not_active Ceased
- 2015-06-17 US US14/742,159 patent/US9272019B2/en not_active Expired - Fee Related
- 2015-06-23 AR ARP150102007A patent/AR100945A1/es active IP Right Grant
2016
- 2016-01-19 US US15/000,637 patent/US9956264B2/en not_active Expired - Fee Related
- 2016-11-28 ZA ZA2016/08214A patent/ZA201608214B/en unknown
- 2016-12-01 IL IL249327A patent/IL249327A0/en unknown

Also Published As

Publication number	Publication date
RU2017101436A (ru)	2018-07-24
TW201613958A (en)	2016-04-16
JP2017528419A (ja)	2017-09-28
BR112016029848A2 (pt)	2017-10-24
CN106459222A (zh)	2017-02-22
WO2015197446A1 (en)	2015-12-30
MX2016016063A (es)	2017-03-10
RU2017101436A3 (2)	2019-02-13
EP3160496B1 (en)	2021-03-03
EP3160496A1 (en)	2017-05-03
AU2015279525A1 (en)	2016-12-15
JP6696915B2 (ja)	2020-05-20
US9956264B2 (en)	2018-05-01
US20160129083A1 (en)	2016-05-12
US20160015784A1 (en)	2016-01-21
US9272019B2 (en)	2016-03-01
ZA201608214B (en)	2018-11-28
KR20170020383A (ko)	2017-02-22
AR100945A1 (es)	2016-11-09
IL249327A0 (en)	2017-02-28

Legal Events

Date	Code	Title	Description
2023-10-24	AZWI	Withdrawn application	Effective date: 20190909

Publication	Publication Date	Title
US9956264B2 (en)	2018-05-01	MIC-1 fusion proteins and uses thereof
US12006344B2 (en)	2024-06-11	MIC-1 compounds and use thereof
KR102085605B1 (ko)	2020-03-06	대사 장애를 치료하기 위한 융합 단백질
JP6110304B2 (ja)	2017-04-05	Ｆｇｆ２１関連障害を処置する方法
KR102217254B1 (ko)	2021-02-19	대사 장애를 치료하기 위한 이중 기능 단백질
US8809499B2 (en)	2014-08-19	Fusion protein of human fibroblast growth factor-21 and exendin-4
CA2871145A1 (en)	2013-12-19	Fibroblast growth factor 21 proteins
EP3237441A1 (en)	2017-11-01	Methods of improving yield in recombinant protein production
US20170334971A1 (en)	2017-11-23	Alpha-1-Antitrypsin (A1AT) Fusion Proteins and Uses Thereof
KR20240126875A (ko)	2024-08-21	Glp-1과 gdf15의 융합 단백질 및 이의 용도
RU2776529C2 (ru)	2022-07-21	Соединения mic-1 и их применение