CN101199483B - Stable anti-HER2 humanized antibody preparation - Google Patents
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- CN101199483B CN101199483B CN2006101472804A CN200610147280A CN101199483B CN 101199483 B CN101199483 B CN 101199483B CN 2006101472804 A CN2006101472804 A CN 2006101472804A CN 200610147280 A CN200610147280 A CN 200610147280A CN 101199483 B CN101199483 B CN 101199483B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- 239000004094 surface-active agent Substances 0.000 claims abstract description 8
- 239000003223 protective agent Substances 0.000 claims abstract description 7
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 16
- 229960002885 histidine Drugs 0.000 claims description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 229930006000 Sucrose Natural products 0.000 claims description 9
- 239000005720 sucrose Substances 0.000 claims description 9
- 239000000872 buffer Substances 0.000 claims description 8
- 239000011780 sodium chloride Substances 0.000 claims description 8
- CMXXUDSWGMGYLZ-XRIGFGBMSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride;hydrate Chemical compound O.Cl.OC(=O)[C@@H](N)CC1=CN=CN1 CMXXUDSWGMGYLZ-XRIGFGBMSA-N 0.000 claims description 7
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 7
- 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 claims description 7
- 238000009472 formulation Methods 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 7
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 7
- HNYSIKXAASZNEM-JEDNCBNOSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydrate Chemical compound O.OC(=O)[C@@H](N)CC1=CNC=N1 HNYSIKXAASZNEM-JEDNCBNOSA-N 0.000 claims description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 5
- 229920000053 polysorbate 80 Polymers 0.000 claims description 5
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 4
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 4
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 4
- 230000003139 buffering effect Effects 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229940105067 sodium chloride 9 mg/ml Drugs 0.000 claims description 2
- 125000000185 sucrose group Chemical group 0.000 claims description 2
- 239000006172 buffering agent Substances 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 description 5
- 230000002018 overexpression Effects 0.000 description 4
- 239000011550 stock solution Substances 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- -1 Polyoxyethylene Polymers 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000008521 reorganization Effects 0.000 description 2
- 239000011265 semifinished product Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 150000003625 trehaloses Chemical class 0.000 description 2
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 description 1
- QAWLKTDBUQOFEF-UHFFFAOYSA-N 3-(4-bromophenyl)propanenitrile Chemical compound BrC1=CC=C(CCC#N)C=C1 QAWLKTDBUQOFEF-UHFFFAOYSA-N 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000002270 exclusion chromatography Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 229940116978 human epidermal growth factor Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 239000004223 monosodium glutamate Substances 0.000 description 1
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011125 single therapy Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
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- 229960001603 tamoxifen Drugs 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a humanized anti-HER2 antibody preparation, which contains humanized anti-HER2 antibody, protective agent, buffering agent, surfactant and isotonic regulator. The invention has the advantages of stability and low price.
Description
Technical field
The invention belongs to biological technical field, more specifically, the invention discloses a kind of stable biological preparation.
Background technology
Humanized Anti-HER 2 is the deutero-Humanized monoclonal antibodies of a kind of recombinant DNA, optionally acts on the position, extracellular of human epidermal growth factor acceptor-2 (HER2).This antibody belongs to the IgG1 type, contain the people framework region and can with the complementary determining region of the bonded mouse-anti of HER2-p185HER2 antibody, in external and zoopery, all show the propagation of the tumor cell can suppress the HER2 overexpression.In addition, this antibody is the potential medium of the cell-mediated cytotoxic reaction (ADCC) of antibody dependence, and in vitro study, this antibody-mediated ADCC is proved to be in the cancerous cell of HER2 overexpression than more preferably producing in the cancerous cell of the non-overexpression of HER2.Gone on the market by drugs approved by FDA at present, as the metastatic breast cancer of single therapy HER2 overexpression.
The preparation that is applied to clinical humanized Anti-HER 2 is a lyophilized formulations, its excipient is the L-histidine monohydrochloride, the L-histidine, α, α-two carboxylic trehaloses, Polyoxyethylene Sorbitol Fatty Acid Esters 20, this preparation is not only not really stable, should not place for a long time, and the α of its use, α-two carboxylic trehaloses cost an arm and a leg, and have increased patient's drug cost.
Summary of the invention
In order to address the above problem, applicant of the present invention has carried out a large amount of experiments, has obtained a kind of preparation of stable, inexpensive anti-HER 2 humanized antibody.
Particularly:
The invention discloses a kind of anti-HER 2 humanized antibody preparation, form by anti-HER 2 humanized antibody, protective agent, buffer agent, surfactant and isoosmotic adjusting agent.
Above-mentioned anti-HER 2 humanized antibody preparation disclosed by the invention is lyophilized formulations.
Above-mentioned anti-HER 2 humanized antibody preparation disclosed by the invention; wherein each components contents is anti-HER 2 humanized antibody 10～40mg/ml, protective agent 10～100mg/ml, buffer agent 3～10mmol; surfactant 0.05～0.2mg/ml, isoosmotic adjusting agent 2～9mg/ml.
Above-mentioned anti-HER 2 humanized antibody preparation disclosed by the invention, wherein protective agent is one of nonreducing sugar, monosodium glutamate, histidine, trihydroxylic alcohol or its combination.
Above-mentioned anti-HER 2 humanized antibody preparation disclosed by the invention, wherein nonreducing sugar is sucrose or trehalose.
Above-mentioned anti-HER 2 humanized antibody preparation disclosed by the invention, wherein buffer agent is histidine or succinic acid buffer.
Above-mentioned anti-HER 2 humanized antibody preparation disclosed by the invention, wherein buffer agent is a histidine buffering liquid.
Above-mentioned anti-HER 2 humanized antibody preparation disclosed by the invention, wherein surfactant is a tween 20.
Above-mentioned anti-HER 2 humanized antibody preparation disclosed by the invention, wherein isoosmotic adjusting agent is a sodium chloride.
Above-mentioned anti-HER 2 humanized antibody preparation disclosed by the invention; wherein the content of anti-HER 2 humanized antibody is 20mg/ml, and protectant content is 38mg/ml, and the content of buffer agent is 4.44mmol; the content of surfactant is 0.09mg/ml, and the content of isoosmotic adjusting agent is 4mg/ml.
Above-mentioned preparation disclosed by the invention, preferred lyophilized formulations, these lyophilized formulations are according to Pharmacopoeia of the People's Republic of China version in 2005, two appendix XIX C crude drug and pharmaceutical preparation stability test guideline have been carried out stability experiment, experimental result shows, preparation disclosed by the invention 4 ℃ preserve more than 3 years or 30 ℃ preserve that biological activity remains on more than 95% more than 1 year, lyophilized formulations disclosed by the invention is rebuild with 0.9% or 1.1% benzyl alcohol, preparation after the reconstruction was preserved 3 months at 2～8 ℃, biological activity remains on more than 93%, has reached purpose of the present invention.
The specific embodiment
Further specify the present invention below in conjunction with embodiment, experimental example, following embodiment, experimental example should not be construed as limitation of the present invention.
Anti-HER 2 humanized antibody: it prepares with reference to Carter P, Presta L, Gorman CM, RidgwayJB, Henner D, Wong WL, Rowland AM, Kotts C, Carver ME, Shepard HM.ProcNatl Acad Sci U S is May 15 A.1992; 89 (10): 4285-9.Humanization of ananti-p185HER2 antibody for human cancer therapy.Anti-HER 2 humanized antibody of the present invention is not limited only to that this is a kind of, and those skilled in the art utilizes anti-HER 2 humanized antibody that general technique for gene engineering obtains also at the row of anti-HER 2 humanized antibody of the present invention.
Unless stated otherwise, other supplementary material is commercially available pharmaceutic adjuvant rank.
The preparation of the preparation of embodiment anti-HER 2 humanized antibody
Embodiment 1
Prescription:
Amounts of components
Anti-HER 2 humanized antibody 20mg/ml
Sucrose 38mg/ml
L-histidine 0.32mg/ml
L-histidine hydrochloride monohydrate 0.5mg/ml
Tween 20 0.09mg/ml
Sodium chloride 4mg/ml
Preparation process:
Molecular exclusion chromatography is adopted in the anti-HER 2 humanized monoclonal antibody purification final step of recombinating, and mobile phase is:
L-histidine 0.32mg/ml
L-histidine hydrochloride monohydrate 0.5mg/ml
Sodium chloride 4mg/ml
Through the stock solution of the anti-HER 2 humanized monoclonal antibody of this step purification acquisition reorganization, the concentration of the anti-HER 2 humanized monoclonal antibody of reorganization should be greater than 20mg/ml in the stock solution.
The preparation of preparation:
According to the required sucrose of the volume calculation of stock solution and the consumption (final concentration is respectively 38mg/ml and 0.09mg/ml) of tween 20, and add in the stock solution.
Adjust the concentration of all components in the solution, make each constituent content as follows:
Amounts of components
Anti-HER 2 humanized antibody 20mg/ml
Sucrose 38mg/ml
L-histidine 0.32mg/ml
L-histidine hydrochloride monohydrate 0.5mg/ml
Tween 20 0.09mg/ml
Sodium chloride 4mg/ml
Obtain semi-finished product, go in the cillin bottle semi-finished product are aseptic subpackaged, add a cover rubber stopper, aluminium-plastic cap is added a cover in lyophilization, obtains finished product.
Embodiment 2
Prescription:
Amounts of components
Anti-HER 2 humanized antibody 10mg/ml
Sucrose 10mg/ml
L-histidine 0.16mg/ml
L-histidine hydrochloride monohydrate 0.25mg/ml
Tween 20 0.05mg/ml
Preparation method is with embodiment 1.
Embodiment 3:
Prescription
Constituent content
Anti-HER 2 humanized antibody 20mg/ml,
Sucrose 50mg/ml
L-histidine 0.32mg/ml
L-histidine monohydrate 0.5mg/ml
Tween 80 0.09mg/ml
Sodium chloride 4mg/ml
Preparation method is with embodiment 1.
Experimental example 4
Anti-HER 2 humanized antibody 40mg/ml,
Trehalose 100mg/ml
L-histidine 0.48mg/ml
L-histidine monohydrate 0.75mg/ml
Tween 80 0.2mg/ml
Sodium chloride 9mg/ml
Preparation method is with embodiment 1
The experimental example stability experiment
Each three batches in the resulting sample of embodiment 1-4 carries out stability experiment, and experimental result is as shown in table 1, and wherein respectively three batch samples of obtaining for embodiment 1-4 of NO1-4 are carried out the meansigma methods of result behind the stability experiment.
The external biological activity test method is with reference to Synergistic Interactions between Tamoxifen andTrastuzumab (Herceptin) .Athanassios Argiris, Chun-Xia Wang, Steve G.Whalenand Michael P.DiGiovanna, Clin Cancer Res.2004 Feb 15; 10 (4): 1409-20, carry out.
Table 1: the active result of external biological
| Preservation condition | ?No.1 | NO.2 | NO.3 | NO.4 |
| 4 ℃, lucifuge, 3 years | ?102％ | 94％ | 97％ | 96％ |
| 30 ℃, lucifuge, 1 year | ?97％ | 91％ | 96％ | 95％ |
| Reconstituted formulation, 2-8 ℃, 3 months | ?98％ | 85％ | 95％ | 93％ |
Claims (4)
1. preparation that contains anti-HER 2 humanized antibody; by anti-HER 2 humanized antibody; protective agent; buffer agent; surfactant and isoosmotic adjusting agent are formed; wherein protective agent is sucrose or trehalose; buffer agent is the histidine buffering liquid of being made up of L-histidine and L-histidine hydrochloride monohydrate or L-histidine monohydrate; isoosmotic adjusting agent is a sodium chloride; surfactant is tween 20 or tween 80; wherein each components contents is anti-HER 2 humanized antibody 10～40mg/ml; protective agent 10～100mg/ml; L-histidine 0.16-0.48mg/ml; L-histidine hydrochloride monohydrate or L-histidine monohydrate are 0.25-0.75mg/ml; surfactant 0.05～0.2mg/ml; isoosmotic adjusting agent 2～9mg/ml, described preparation are lyophilized formulations.
2. the described preparation of claim 1, wherein each components contents is anti-HER 2 humanized antibody 20mg/ml, sucrose 38mg/ml, L-histidine 0.32mg/ml, L-histidine hydrochloride monohydrate 0.5mg/ml, tween 20 0.09mg/ml, sodium chloride 4mg/ml.
3. the described preparation of claim 1, wherein each components contents is anti-HER 2 humanized antibody 20mg/ml, sucrose 50mg/ml, L-histidine 0.32mg/ml, L-histidine monohydrate 0.5mg/ml, tween 80 0.09mg/ml, sodium chloride 4mg/ml.
4. the described preparation of claim 1, wherein each components contents is anti-HER 2 humanized antibody 40mg/ml, trehalose 100mg/ml, L-histidine 0.48mg/ml, L-histidine monohydrate 0.75mg/ml, tween 80 0.2mg/ml, sodium chloride 9mg/ml.
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| CN2006101472804A CN101199483B (en) | 2006-12-14 | 2006-12-14 | Stable anti-HER2 humanized antibody preparation |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006101472804A CN101199483B (en) | 2006-12-14 | 2006-12-14 | Stable anti-HER2 humanized antibody preparation |
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| CN101199483B true CN101199483B (en) | 2011-01-26 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10000573B2 (en) | 2008-03-14 | 2018-06-19 | Centro De Immunologia Molecular | Monoclonal antibody and a method thereof |
| US10189899B2 (en) | 2013-07-23 | 2019-01-29 | Biocon Limited | Use of a CD6 binding partner and method based thereon |
| US11242401B2 (en) | 2016-10-21 | 2022-02-08 | Biocon Limited | Monoclonal antibody and a method of use for the treatment of lupus |
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| EP3721904B1 (en) * | 2009-11-20 | 2021-10-13 | Biocon Limited | Formulations of t1h antibody |
| AU2016280159A1 (en) * | 2015-06-17 | 2017-12-07 | Genentech, Inc. | Anti-HER2 antibodies and methods of use |
| CN111375057B (en) * | 2018-12-28 | 2024-06-21 | 上海复宏汉霖生物技术股份有限公司 | Pharmaceutical formulation comprising anti-Her 2 monoclonal antibody |
| CN113827717A (en) * | 2020-06-23 | 2021-12-24 | 三生国健药业（上海）股份有限公司 | Anti-HER2 monoclonal antibody freeze-dried preparation and preparation method |
| WO2022261716A1 (en) * | 2021-06-16 | 2022-12-22 | Exopharm Limited | Aqueous formulations for preservation of extracellular vesicles |
| CN113480657B (en) * | 2021-08-06 | 2023-01-20 | 南京融捷康生物科技有限公司 | Single-domain antibody aiming at HER2, and derivative protein and application thereof |
| WO2023165142A1 (en) * | 2022-03-01 | 2023-09-07 | 苏州智核生物医药科技有限公司 | Her2 binding polypeptide and use thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| US6685940B2 (en) * | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
| CN1539505A (en) * | 1995-07-27 | 2004-10-27 | �����ɷ� | Stable isotonic lyophilized protein formulation |
-
2006
- 2006-12-14 CN CN2006101472804A patent/CN101199483B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| US6685940B2 (en) * | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
| CN1539505A (en) * | 1995-07-27 | 2004-10-27 | �����ɷ� | Stable isotonic lyophilized protein formulation |
| US7060268B2 (en) * | 1995-07-27 | 2006-06-13 | Genentech, Inc. | Protein formulation |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10000573B2 (en) | 2008-03-14 | 2018-06-19 | Centro De Immunologia Molecular | Monoclonal antibody and a method thereof |
| US10669346B2 (en) | 2008-03-14 | 2020-06-02 | Biocon Limited | Monoclonal antibody and a method thereof |
| US11981743B2 (en) | 2008-03-14 | 2024-05-14 | Biocon Limited | Monoclonal antibody and a method thereof |
| US10189899B2 (en) | 2013-07-23 | 2019-01-29 | Biocon Limited | Use of a CD6 binding partner and method based thereon |
| US11028168B2 (en) | 2013-07-23 | 2021-06-08 | Biocon Limited | Use of a CD6 binding partner and method based thereon |
| US11242401B2 (en) | 2016-10-21 | 2022-02-08 | Biocon Limited | Monoclonal antibody and a method of use for the treatment of lupus |
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| CN101199483A (en) | 2008-06-18 |
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