CA2616187A1 - Human growth hormone conjugated with biocompatible polymer - Google Patents
Human growth hormone conjugated with biocompatible polymer Download PDFInfo
- Publication number
- CA2616187A1 CA2616187A1 CA002616187A CA2616187A CA2616187A1 CA 2616187 A1 CA2616187 A1 CA 2616187A1 CA 002616187 A CA002616187 A CA 002616187A CA 2616187 A CA2616187 A CA 2616187A CA 2616187 A1 CA2616187 A1 CA 2616187A1
- Authority
- CA
- Canada
- Prior art keywords
- hgh
- peg
- conjugate
- biocompatible polymer
- molar ratio
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 229920000249 biocompatible polymer Polymers 0.000 title claims abstract description 51
- 239000000854 Human Growth Hormone Substances 0.000 title claims description 185
- 108010000521 Human Growth Hormone Proteins 0.000 title description 193
- 102000002265 Human Growth Hormone Human genes 0.000 title description 191
- 238000000034 method Methods 0.000 claims abstract description 40
- 230000000694 effects Effects 0.000 claims abstract description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 206010016165 failure to thrive Diseases 0.000 claims abstract description 7
- 206010053759 Growth retardation Diseases 0.000 claims abstract description 6
- 230000032683 aging Effects 0.000 claims abstract description 6
- 231100000001 growth retardation Toxicity 0.000 claims abstract description 5
- 208000020221 Short stature Diseases 0.000 claims abstract description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 35
- 238000002347 injection Methods 0.000 claims description 31
- 239000007924 injection Substances 0.000 claims description 31
- 108090000623 proteins and genes Proteins 0.000 claims description 20
- 102000004169 proteins and genes Human genes 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims description 12
- 125000000524 functional group Chemical group 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 10
- 230000008878 coupling Effects 0.000 claims description 9
- 238000010168 coupling process Methods 0.000 claims description 9
- 238000005859 coupling reaction Methods 0.000 claims description 9
- 230000007812 deficiency Effects 0.000 claims description 7
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 6
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 6
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 6
- 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 claims description 6
- 238000004587 chromatography analysis Methods 0.000 claims description 6
- 230000007423 decrease Effects 0.000 claims description 6
- 210000003205 muscle Anatomy 0.000 claims description 6
- 229920002538 Polyethylene Glycol 20000 Polymers 0.000 claims description 5
- 208000026928 Turner syndrome Diseases 0.000 claims description 5
- 208000030507 AIDS Diseases 0.000 claims description 4
- 210000000577 adipose tissue Anatomy 0.000 claims description 4
- 208000020832 chronic kidney disease Diseases 0.000 claims description 4
- 238000004255 ion exchange chromatography Methods 0.000 claims description 4
- 206010006895 Cachexia Diseases 0.000 claims description 3
- 230000003213 activating effect Effects 0.000 claims description 3
- 230000002421 anti-septic effect Effects 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 235000012000 cholesterol Nutrition 0.000 claims description 3
- 230000001268 conjugating effect Effects 0.000 claims description 3
- 230000002411 adverse Effects 0.000 claims description 2
- 125000000129 anionic group Chemical group 0.000 claims description 2
- 230000036772 blood pressure Effects 0.000 claims description 2
- 230000037182 bone density Effects 0.000 claims description 2
- 239000005556 hormone Substances 0.000 claims description 2
- 229940088597 hormone Drugs 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 15
- 238000001727 in vivo Methods 0.000 abstract description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 26
- 241000700159 Rattus Species 0.000 description 24
- 239000000122 growth hormone Substances 0.000 description 24
- 102000018997 Growth Hormone Human genes 0.000 description 22
- 108010051696 Growth Hormone Proteins 0.000 description 22
- 230000037396 body weight Effects 0.000 description 19
- 230000002354 daily effect Effects 0.000 description 16
- 229920000642 polymer Polymers 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 14
- 230000004071 biological effect Effects 0.000 description 11
- 238000011282 treatment Methods 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 239000011149 active material Substances 0.000 description 10
- 230000012010 growth Effects 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000003636 conditioned culture medium Substances 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 230000001580 bacterial effect Effects 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- -1 polyoxyethylene Polymers 0.000 description 8
- 239000013641 positive control Substances 0.000 description 8
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 239000007983 Tris buffer Substances 0.000 description 6
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 6
- 238000001516 cell proliferation assay Methods 0.000 description 6
- 230000021615 conjugation Effects 0.000 description 6
- 229920000233 poly(alkylene oxides) Polymers 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- 235000019786 weight gain Nutrition 0.000 description 6
- 239000012614 Q-Sepharose Substances 0.000 description 5
- 239000008186 active pharmaceutical agent Substances 0.000 description 5
- 238000004166 bioassay Methods 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 229940088679 drug related substance Drugs 0.000 description 5
- 230000006320 pegylation Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- 206010056438 Growth hormone deficiency Diseases 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 238000010254 subcutaneous injection Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 230000004584 weight gain Effects 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000012564 Q sepharose fast flow resin Substances 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000007822 coupling agent Substances 0.000 description 3
- 230000007717 exclusion Effects 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 238000009578 growth hormone therapy Methods 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000021332 multicellular organism growth Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- 150000003077 polyols Chemical class 0.000 description 3
- 230000036515 potency Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 2
- 241000701959 Escherichia virus Lambda Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 101710137500 T7 RNA polymerase Proteins 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 238000011210 chromatographic step Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 238000003391 densitometric scan Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229940065770 humatrope Drugs 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 229940102223 injectable solution Drugs 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000001320 lysogenic effect Effects 0.000 description 2
- 230000008774 maternal effect Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920001451 polypropylene glycol Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- MWOOKDULMBMMPN-UHFFFAOYSA-N 3-(2-ethyl-1,2-oxazol-2-ium-5-yl)benzenesulfonate Chemical compound O1[N+](CC)=CC=C1C1=CC=CC(S([O-])(=O)=O)=C1 MWOOKDULMBMMPN-UHFFFAOYSA-N 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 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 1
- 241000282412 Homo Species 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000015580 Increased body weight Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000007987 MES buffer Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 201000010769 Prader-Willi syndrome Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 208000010399 Wasting Syndrome Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 210000004198 anterior pituitary gland Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000001266 bandaging Methods 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
- 108010051210 beta-Fructofuranosidase Proteins 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000008473 connective tissue growth Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 108010005905 delta-hGHR Proteins 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000010217 densitometric analysis Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000001573 invertase Substances 0.000 description 1
- 235000011073 invertase Nutrition 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229920001427 mPEG Polymers 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000037257 muscle growth Effects 0.000 description 1
- OWIUPIRUAQMTTK-UHFFFAOYSA-M n-aminocarbamate Chemical compound NNC([O-])=O OWIUPIRUAQMTTK-UHFFFAOYSA-M 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 231100001223 noncarcinogenic Toxicity 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229940063149 nutropin Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000021368 organ growth Effects 0.000 description 1
- 239000006259 organic additive Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000006353 oxyethylene group Chemical group 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000010773 plant oil Substances 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000009645 skeletal growth Effects 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 108700031632 somatrem Proteins 0.000 description 1
- 229960004532 somatropin Drugs 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000003021 water soluble solvent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Classifications
-
- 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
-
- 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
- C07K14/575—Hormones
- C07K14/61—Growth hormone [GH], i.e. somatotropin
-
- 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
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH], i.e. somatotropin
-
- 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
- A61K47/56—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Endocrinology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physical Education & Sports Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Obesity (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Child & Adolescent Psychology (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/187,522 US20050281778A1 (en) | 2003-03-28 | 2005-07-22 | Human growth hormone conjugated with biocompatible polymer |
| US11/187,522 | 2005-07-22 | ||
| PCT/US2005/046791 WO2007018583A2 (en) | 2005-07-22 | 2005-12-20 | Human growth hormone conjugated with biocompatible polymer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2616187A1 true CA2616187A1 (en) | 2007-02-15 |
Family
ID=36808363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002616187A Abandoned CA2616187A1 (en) | 2005-07-22 | 2005-12-20 | Human growth hormone conjugated with biocompatible polymer |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20050281778A1 (https=) |
| EP (1) | EP1915179A2 (https=) |
| JP (1) | JP2009502779A (https=) |
| KR (1) | KR20080041661A (https=) |
| AU (1) | AU2005335186A1 (https=) |
| CA (1) | CA2616187A1 (https=) |
| WO (1) | WO2007018583A2 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7547445B2 (en) * | 1998-03-19 | 2009-06-16 | Surmodics, Inc. | Crosslinkable macromers |
| WO2006102659A2 (en) * | 2005-03-23 | 2006-09-28 | Nektar Therapeutics Al, Corporation | CONJUGATES OF AN hGH MOIETY AND A POLYMER |
| US9840546B2 (en) * | 2008-04-03 | 2017-12-12 | Biosteed Gene Expression Tech. Co., Ltd. | Double-stranded polyethylene glycol modified growth hormone, preparation method and application thereof |
| US10064951B2 (en) | 2012-03-30 | 2018-09-04 | Hanmi Science Co., Ltd. | Liquid formulation of highly concentrated long-acting human growth hormone conjugate |
| CN116421566B (zh) * | 2023-02-16 | 2024-10-22 | 高邮市人民医院 | 一种含聚乙二醇化重组人生长激素的制剂 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0401384B1 (en) * | 1988-12-22 | 1996-03-13 | Kirin-Amgen, Inc. | Chemically modified granulocyte colony stimulating factor |
| US5766897A (en) * | 1990-06-21 | 1998-06-16 | Incyte Pharmaceuticals, Inc. | Cysteine-pegylated proteins |
| US5951974A (en) * | 1993-11-10 | 1999-09-14 | Enzon, Inc. | Interferon polymer conjugates |
| US5597709A (en) * | 1994-01-27 | 1997-01-28 | Human Genome Sciences, Inc. | Human growth hormone splice variants hGHV-2(88) and hGHV-3(53) |
| US5985263A (en) * | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
| US20030171285A1 (en) * | 2001-11-20 | 2003-09-11 | Finn Rory F. | Chemically-modified human growth hormone conjugates |
| AP2004003050A0 (en) * | 2001-11-20 | 2004-06-30 | Pharmacia Corp | Chemically modified human growth hormone conjugates |
-
2005
- 2005-07-22 US US11/187,522 patent/US20050281778A1/en not_active Abandoned
- 2005-12-20 KR KR1020087004205A patent/KR20080041661A/ko not_active Withdrawn
- 2005-12-20 CA CA002616187A patent/CA2616187A1/en not_active Abandoned
- 2005-12-20 EP EP05855362A patent/EP1915179A2/en not_active Withdrawn
- 2005-12-20 WO PCT/US2005/046791 patent/WO2007018583A2/en not_active Ceased
- 2005-12-20 JP JP2008522759A patent/JP2009502779A/ja active Pending
- 2005-12-20 AU AU2005335186A patent/AU2005335186A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2005335186A1 (en) | 2007-02-15 |
| WO2007018583A2 (en) | 2007-02-15 |
| JP2009502779A (ja) | 2009-01-29 |
| EP1915179A2 (en) | 2008-04-30 |
| US20050281778A1 (en) | 2005-12-22 |
| KR20080041661A (ko) | 2008-05-13 |
| WO2007018583A3 (en) | 2007-05-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7893019B2 (en) | G-CSF site-specific mono-conjugates | |
| EP1037657B1 (en) | Alpha-interferon-polymer-conjugates having enhanced biological activity and methods of preparing the same | |
| US5738846A (en) | Interferon polymer conjugates and process for preparing the same | |
| US5711944A (en) | Interferon polymer conjugates | |
| CN104043107B (zh) | 一种治疗肿瘤的药物及其应用 | |
| US20030054997A1 (en) | OB protein compositions and methods | |
| JP2006321808A (ja) | 化学的に修飾されたヒト成長ホルモンコンジュゲート | |
| CN101812438B (zh) | 一种精氨酸脱亚氨酶突变体及其制备与应用 | |
| US20030171285A1 (en) | Chemically-modified human growth hormone conjugates | |
| JP5458416B2 (ja) | 二本鎖ポリエチレングリコール化成長ホルモン、その製造方法およびその使用 | |
| JP2006521372A (ja) | 生物学的活性物質と生体適合性高分子の１：１接合体、この製造方法とこれを含む薬学組成物 | |
| US20040038892A1 (en) | Chemically-modified human growth hormone conjugates | |
| CA2616187A1 (en) | Human growth hormone conjugated with biocompatible polymer | |
| CN101591649B (zh) | 甲氧基聚乙二醇修饰的精氨酸脱亚氨酶及其制备与应用 | |
| US20060134736A1 (en) | Human growth hormone conjugated with biocompatible polymer | |
| US20090203589A1 (en) | Chemically modified human growth hormone receptor antagonist conjugates | |
| CN101163716B (zh) | 白细胞介素-6聚乙二醇结合物及其制备方法和应用 | |
| CN116212040B (zh) | 一种作为Treg靶向调节剂的PEG修饰IL-2的组合物及其制备方法和用途 | |
| CN113121649B (zh) | 一种新型两亲性蛋白、其制备方法及用途 | |
| KR20040086522A (ko) | 부갑상성 호르몬과 생체적합성 고분자의 1:1 접합체,이의 제조방법과 이를 함유하는 약학 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |