JP2017225444A5 - - Google Patents
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- JP2017225444A5 JP2017225444A5 JP2017133655A JP2017133655A JP2017225444A5 JP 2017225444 A5 JP2017225444 A5 JP 2017225444A5 JP 2017133655 A JP2017133655 A JP 2017133655A JP 2017133655 A JP2017133655 A JP 2017133655A JP 2017225444 A5 JP2017225444 A5 JP 2017225444A5
- Authority
- JP
- Japan
- Prior art keywords
- human
- igf
- crosslinker
- modified
- lysosomal enzyme
- 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.)
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- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 claims description 46
- 239000004971 Cross linker Substances 0.000 claims description 30
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 17
- 101001018026 Homo sapiens Lysosomal alpha-glucosidase Proteins 0.000 claims description 14
- 102000045921 human GAA Human genes 0.000 claims description 14
- 235000001014 amino acid Nutrition 0.000 claims description 13
- 150000001413 amino acids Chemical class 0.000 claims description 13
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 10
- 239000000872 buffer Substances 0.000 claims description 10
- 239000004472 Lysine Substances 0.000 claims description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 7
- 230000008878 coupling Effects 0.000 claims description 7
- 238000010168 coupling process Methods 0.000 claims description 7
- 238000005859 coupling reaction Methods 0.000 claims description 7
- -1 oxa pentadecane acetylene Chemical group 0.000 claims description 7
- 239000004471 Glycine Substances 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 5
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- OIGKWPIMJCPGGD-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]propanoate Chemical compound [N-]=[N+]=NCCOCCOCCOCCOCCC(=O)ON1C(=O)CCC1=O OIGKWPIMJCPGGD-UHFFFAOYSA-N 0.000 claims description 3
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 3
- 125000000539 amino acid group Chemical group 0.000 claims description 3
- 102000004190 Enzymes Human genes 0.000 claims 18
- 108090000790 Enzymes Proteins 0.000 claims 18
- 230000002132 lysosomal effect Effects 0.000 claims 18
- 238000006467 substitution reaction Methods 0.000 claims 14
- 239000002253 acid Substances 0.000 claims 11
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 11
- 238000012217 deletion Methods 0.000 claims 8
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- 239000003431 cross linking reagent Substances 0.000 claims 7
- 125000005647 linker group Chemical group 0.000 claims 7
- 239000004475 Arginine Substances 0.000 claims 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims 4
- 208000015439 Lysosomal storage disease Diseases 0.000 claims 4
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims 4
- 239000004473 Threonine Substances 0.000 claims 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 4
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims 4
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 claims 4
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims 4
- 125000000341 threoninyl group Chemical class [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 claims 4
- GVJXGCIPWAVXJP-UHFFFAOYSA-N 2,5-dioxo-1-oxoniopyrrolidine-3-sulfonate Chemical compound ON1C(=O)CC(S(O)(=O)=O)C1=O GVJXGCIPWAVXJP-UHFFFAOYSA-N 0.000 claims 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Natural products CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 2
- 101000962729 Dictyostelium discoideum Lysosomal alpha-mannosidase Proteins 0.000 claims 2
- 102000053187 Glucuronidase Human genes 0.000 claims 2
- 108010060309 Glucuronidase Proteins 0.000 claims 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims 2
- 101000718525 Homo sapiens Alpha-galactosidase A Proteins 0.000 claims 2
- 101000997662 Homo sapiens Lysosomal acid glucosylceramidase Proteins 0.000 claims 2
- 101000585728 Homo sapiens Protein O-GlcNAcase Proteins 0.000 claims 2
- 102000004882 Lipase Human genes 0.000 claims 2
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- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 2
- 230000001268 conjugating effect Effects 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 229930195712 glutamate Natural products 0.000 claims 2
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical class N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 claims 2
- 235000013922 glutamic acid Nutrition 0.000 claims 2
- 239000004220 glutamic acid Substances 0.000 claims 2
- 125000000291 glutamic acid group Chemical class N[C@@H](CCC(O)=O)C(=O)* 0.000 claims 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims 2
- 102000043404 human GLA Human genes 0.000 claims 2
- 238000012986 modification Methods 0.000 claims 2
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- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims 2
- 125000001493 tyrosinyl group Chemical class [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 2
- 239000004474 valine Substances 0.000 claims 2
- 125000002987 valine group Chemical class [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- VDVAKFCNFMDCPL-UHFFFAOYSA-N 1-(2,5-dioxopyrrolidin-1-yl)-6-hydrazinyl-2H-pyridine-3-carboxylic acid propan-2-one Chemical compound CC(C)=O.NNC1=CC=C(CN1N1C(=O)CCC1=O)C(O)=O VDVAKFCNFMDCPL-UHFFFAOYSA-N 0.000 claims 1
- 208000024720 Fabry Disease Diseases 0.000 claims 1
- 208000015872 Gaucher disease Diseases 0.000 claims 1
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 claims 1
- 206010053185 Glycogen storage disease type II Diseases 0.000 claims 1
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 claims 1
- 208000026589 Wolman disease Diseases 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 102000005840 alpha-Galactosidase Human genes 0.000 claims 1
- 108010030291 alpha-Galactosidase Proteins 0.000 claims 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims 1
- 201000008333 alpha-mannosidosis Diseases 0.000 claims 1
- 230000001588 bifunctional effect Effects 0.000 claims 1
- 238000012412 chemical coupling Methods 0.000 claims 1
- URYYVOIYTNXXBN-UPHRSURJSA-N cyclooctene Chemical compound C1CCC\C=C/CC1 URYYVOIYTNXXBN-UPHRSURJSA-N 0.000 claims 1
- 239000004913 cyclooctene Substances 0.000 claims 1
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- 208000022018 mucopolysaccharidosis type 2 Diseases 0.000 claims 1
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
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- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 230000021615 conjugation Effects 0.000 description 3
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- 239000001488 sodium phosphate Substances 0.000 description 3
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
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- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
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- 102100037182 Cation-independent mannose-6-phosphate receptor Human genes 0.000 description 1
- 101710145225 Cation-independent mannose-6-phosphate receptor Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
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- 125000003277 amino group Chemical group 0.000 description 1
- 230000004700 cellular uptake Effects 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
- 125000005597 hydrazone group Chemical group 0.000 description 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161490957P | 2011-05-27 | 2011-05-27 | |
| US61/490,957 | 2011-05-27 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014513625A Division JP6300720B2 (ja) | 2011-05-27 | 2012-05-25 | リソソーム蓄積症の改善された治療のための組換えリソソーム酵素にターゲティングペプチドをカップリングするための方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017225444A JP2017225444A (ja) | 2017-12-28 |
| JP2017225444A5 true JP2017225444A5 (enExample) | 2019-06-27 |
Family
ID=47260229
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014513625A Active JP6300720B2 (ja) | 2011-05-27 | 2012-05-25 | リソソーム蓄積症の改善された治療のための組換えリソソーム酵素にターゲティングペプチドをカップリングするための方法 |
| JP2017133655A Pending JP2017225444A (ja) | 2011-05-27 | 2017-07-07 | リソソーム蓄積症の改善された治療のための組換えリソソーム酵素にターゲティングペプチドをカップリングするための方法 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014513625A Active JP6300720B2 (ja) | 2011-05-27 | 2012-05-25 | リソソーム蓄積症の改善された治療のための組換えリソソーム酵素にターゲティングペプチドをカップリングするための方法 |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US9545450B2 (enExample) |
| EP (1) | EP2714752B1 (enExample) |
| JP (2) | JP6300720B2 (enExample) |
| KR (2) | KR20190022943A (enExample) |
| CN (2) | CN104160033B (enExample) |
| BR (1) | BR112013030432A2 (enExample) |
| CA (1) | CA2836318C (enExample) |
| CY (1) | CY1120485T1 (enExample) |
| DK (1) | DK2714752T3 (enExample) |
| ES (1) | ES2660185T3 (enExample) |
| HR (1) | HRP20180291T1 (enExample) |
| HU (1) | HUE038172T2 (enExample) |
| LT (1) | LT2714752T (enExample) |
| NO (1) | NO2820016T3 (enExample) |
| PL (1) | PL2714752T3 (enExample) |
| PT (1) | PT2714752T (enExample) |
| RS (1) | RS56913B1 (enExample) |
| SI (1) | SI2714752T1 (enExample) |
| SM (1) | SMT201800101T1 (enExample) |
| TR (1) | TR201802230T4 (enExample) |
| WO (1) | WO2012166653A2 (enExample) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9925303B2 (en) * | 2012-11-13 | 2018-03-27 | Edwards Lifesciences Corporation | Methods for cross-linking bioprosthetic tissue using bio-orthogonal binding pairs |
| CA2902210C (en) * | 2013-03-15 | 2021-07-20 | Amicus Therapeutics, Inc. | Chemical crosslinkers |
| AU2015240516C1 (en) * | 2014-04-04 | 2019-04-11 | Vestaron Corporation | Artificially activated peptides |
| AU2015301809A1 (en) * | 2014-08-11 | 2017-02-02 | Shire Human Genetic Therapies, Inc. | Mannose-6-phosphate bearing peptides fused to lysosomal enzymes |
| SI4273241T1 (sl) * | 2014-09-30 | 2025-03-31 | Amicus Therapeutics, Inc. | Zelo močna kislinska alfa-glukozidaza z okrepljenimi ogljikovimi hidrati |
| CN104356238B (zh) * | 2014-10-15 | 2018-01-09 | 大连理工大学 | 一种重组蛋白a亲和配基的定点固定化方法 |
| US10525495B2 (en) * | 2015-03-11 | 2020-01-07 | Ocv Intellectual Capital, Llc | Methods and systems for filling mufflers with fibrous material |
| CN108474788A (zh) * | 2015-11-06 | 2018-08-31 | 生物马林药物股份有限公司 | 用于检测中和溶酶体酶的摄取的抗体或其它因子的基于细胞的测定 |
| DK3782639T3 (da) * | 2015-12-08 | 2022-08-29 | Regeneron Pharma | Sammensætninger og fremgangsmåder til internalisering af enzymer |
| MA50546A (fr) | 2017-06-07 | 2020-09-16 | Regeneron Pharma | Compositions et méthodes pour l'internalisation d'enzymes |
| KR20200018483A (ko) | 2017-06-14 | 2020-02-19 | 비로메틱스 아게 | 호흡기 합포체 바이러스에 대한 방어를 위한 고리형 펩티드 |
| WO2019070577A1 (en) | 2017-10-02 | 2019-04-11 | Denali Therapeutics Inc. | FUSION PROTEINS COMPRISING SUBSTITUTE ENZYM THERAPY ENZYMES |
| AU2019218892B2 (en) | 2018-02-07 | 2025-08-14 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for therapeutic protein delivery |
| US11492610B2 (en) | 2018-03-08 | 2022-11-08 | California Institute Of Technology | Sample multiplexing for single-cell RNA sequencing |
| TWI808169B (zh) | 2018-04-30 | 2023-07-11 | 美商阿米庫斯醫療股份有限公司 | 基因治療構築體及使用方法 |
| AU2019269685B2 (en) | 2018-05-17 | 2025-12-04 | Regeneron Pharmaceuticals, Inc. | Anti-CD63 antibodies, conjugates, and uses thereof |
| EA202190999A1 (ru) | 2018-10-10 | 2021-10-15 | Амикус Терапьютикс, Инк. | Композиции на основе полипептидов, стабилизированных с помощью дисульфидной связи, и способы применения |
| US11175228B2 (en) * | 2018-11-28 | 2021-11-16 | Promega Corporation | Reactive peptide labeling |
| CA3123086A1 (en) | 2018-12-19 | 2020-06-25 | The Board Of Trustees Of The Leland Stanford Junior University | Bifunctional molecules for lysosomal targeting and related compositions and methods |
| AU2019408048A1 (en) | 2018-12-20 | 2021-06-24 | Universität Zürich | Lipopeptide building blocks and synthetic virus-like particles |
| US20220193207A1 (en) * | 2019-04-30 | 2022-06-23 | The Trustees Of The University Of Pennsylvania | Compositions useful for treatment of pompe disease |
| CN110373405B (zh) * | 2019-07-24 | 2023-12-15 | 杭州恩和生物科技有限公司 | 一种接枝聚合物的生物酶及其制备方法和固定方法 |
| EP4041284A4 (en) * | 2019-10-10 | 2023-10-18 | Amicus Therapeutics, Inc. | VARIANT OF IGF2 CONSTRUCTS |
| WO2022063990A1 (en) | 2020-09-28 | 2022-03-31 | Dbv Technologies | Particle comprising an rsv-f protein for use in rsv vaccination |
| JP2023551903A (ja) | 2020-12-01 | 2023-12-13 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 組織特異的標的化モチーフを有する新規組成物及びそれを含有する組成物 |
| MX2023012513A (es) | 2021-04-23 | 2023-12-15 | Univ Pennsylvania | Nuevas composiciones con motivos selectivos para el cerebro y composiciones que las contienen. |
| EP4359430A4 (en) | 2021-06-23 | 2025-07-16 | Lycia Therapeutics Inc | BIFUNCTIONAL COMPOUNDS CONTAINING IGF-2 POLYPEPTIDES |
| WO2023288033A1 (en) | 2021-07-14 | 2023-01-19 | Lycia Therapeutics, Inc. | Asgpr cell surface receptor binding compounds and conjugates |
| WO2024130070A2 (en) | 2022-12-17 | 2024-06-20 | The Trustees Of The University Of Pennsylvania | Recombinant aav capsids with cardiac- and skeletal muscle- specific targeting motifs and uses thereof |
| WO2024130067A2 (en) | 2022-12-17 | 2024-06-20 | The Trustees Of The University Of Pennsylvania | Recombinant aav mutant vectors with cardiac and skeletal muscle-specific targeting motifs and compositions containing same |
| WO2025007046A1 (en) | 2023-06-29 | 2025-01-02 | The Trustees Of The University Of Pennsylvania | Mutant aav with central nervous system targeting motifs and compositions containing same |
| WO2025012364A1 (en) | 2023-07-12 | 2025-01-16 | Virometix Ag | Compositions of pneumococcal antigens |
| WO2025106661A1 (en) | 2023-11-14 | 2025-05-22 | The Trustees Of The University Of Pennsylvania | Compositions with cardiac and skeletal musclespecific targeting motifs and uses thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1118334A1 (en) * | 2000-01-11 | 2001-07-25 | Aventis Behring Gesellschaft mit beschränkter Haftung | Method for the production of conjugates and uses thereof for the prevention and treatment of allergic reactions and autoimmune diseases |
| US7560424B2 (en) * | 2001-04-30 | 2009-07-14 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| US20030072761A1 (en) | 2001-10-16 | 2003-04-17 | Lebowitz Jonathan | Methods and compositions for targeting proteins across the blood brain barrier |
| US7355018B2 (en) | 2003-09-30 | 2008-04-08 | Regeneron Pharmaceuticals, Inc. | Modified IGF1 polypeptides with increased stability and potency |
| BRPI0912225A2 (pt) | 2008-05-07 | 2018-03-20 | Zystor Therapeutics, Inc. | peptídeos de direcionamento lisossomais e usos dos mesmos |
| PL3939617T3 (pl) * | 2009-02-13 | 2025-03-17 | Immunomedics, Inc. | Związki pośrednie do wytwarzania koniugatów z wiązaniem rozszczepialnym wewnątrzkomórkowo |
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2012
- 2012-05-25 DK DK12793015.4T patent/DK2714752T3/en active
- 2012-05-25 LT LTEP12793015.4T patent/LT2714752T/lt unknown
- 2012-05-25 JP JP2014513625A patent/JP6300720B2/ja active Active
- 2012-05-25 CN CN201280037051.0A patent/CN104160033B/zh active Active
- 2012-05-25 KR KR1020197005833A patent/KR20190022943A/ko not_active Ceased
- 2012-05-25 SM SM20180101T patent/SMT201800101T1/it unknown
- 2012-05-25 US US14/122,858 patent/US9545450B2/en active Active
- 2012-05-25 KR KR1020137034111A patent/KR101955054B1/ko not_active Expired - Fee Related
- 2012-05-25 CN CN201810440498.1A patent/CN108586621A/zh not_active Withdrawn
- 2012-05-25 PT PT127930154T patent/PT2714752T/pt unknown
- 2012-05-25 PL PL12793015T patent/PL2714752T3/pl unknown
- 2012-05-25 CA CA2836318A patent/CA2836318C/en active Active
- 2012-05-25 HR HRP20180291TT patent/HRP20180291T1/hr unknown
- 2012-05-25 WO PCT/US2012/039705 patent/WO2012166653A2/en not_active Ceased
- 2012-05-25 SI SI201231229T patent/SI2714752T1/en unknown
- 2012-05-25 EP EP12793015.4A patent/EP2714752B1/en active Active
- 2012-05-25 RS RS20180188A patent/RS56913B1/sr unknown
- 2012-05-25 BR BR112013030432A patent/BR112013030432A2/pt not_active Application Discontinuation
- 2012-05-25 ES ES12793015.4T patent/ES2660185T3/es active Active
- 2012-05-25 HU HUE12793015A patent/HUE038172T2/hu unknown
- 2012-05-25 TR TR2018/02230T patent/TR201802230T4/tr unknown
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2013
- 2013-02-25 NO NO13708603A patent/NO2820016T3/no unknown
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2016
- 2016-11-09 US US15/347,006 patent/US10660972B2/en active Active
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2017
- 2017-07-07 JP JP2017133655A patent/JP2017225444A/ja active Pending
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2018
- 2018-02-22 CY CY20181100212T patent/CY1120485T1/el unknown
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