AR106949A1 - Polipéptidos biparatópicos que antagonizan la señalización wnt en células tumorales - Google Patents
Polipéptidos biparatópicos que antagonizan la señalización wnt en células tumoralesInfo
- Publication number
- AR106949A1 AR106949A1 ARP160103720A ARP160103720A AR106949A1 AR 106949 A1 AR106949 A1 AR 106949A1 AR P160103720 A ARP160103720 A AR P160103720A AR P160103720 A ARP160103720 A AR P160103720A AR 106949 A1 AR106949 A1 AR 106949A1
- Authority
- AR
- Argentina
- Prior art keywords
- seq
- cdr1
- cdr2
- cdr3
- syamg
- Prior art date
Links
- 230000011664 signaling Effects 0.000 title 1
- 210000004881 tumor cell Anatomy 0.000 title 1
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 abstract 7
- 108060003951 Immunoglobulin Proteins 0.000 abstract 3
- 102000018358 immunoglobulin Human genes 0.000 abstract 3
- 238000000034 method Methods 0.000 abstract 3
- 229920001184 polypeptide Polymers 0.000 abstract 2
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 2
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 2
- 101001043594 Homo sapiens Low-density lipoprotein receptor-related protein 5 Proteins 0.000 abstract 1
- 101001039199 Homo sapiens Low-density lipoprotein receptor-related protein 6 Proteins 0.000 abstract 1
- 102100021926 Low-density lipoprotein receptor-related protein 5 Human genes 0.000 abstract 1
- 102100040704 Low-density lipoprotein receptor-related protein 6 Human genes 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/22—Immunoglobulins specific features characterized by taxonomic origin from camelids, e.g. camel, llama or dromedary
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- 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)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Reproductive Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Endocrinology (AREA)
- Vascular Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
También secuencias específicas de estos polipéptidos, métodos para su fabricación y métodos para usarlos, que incluyen métodos para el tratamiento de enfermedades, tales como el cáncer. Reivindicación 1: Un polipéptido que se fija específicamente a LRP5 o LRP6, caracterizado porque comprende: un primer dominio variable único de inmunoglobulina seleccionado del grupo de dominios variables únicos de inmunoglobina (i) a (iii) definidos por comprender las siguientes secuencias de CDR: (i): CDR1: TYTVG (= SEQ ID Nº 1), CDR2: AIRRRGSSTYYADSVKG (= SEQ ID Nº 2), CDR3: DTRTVALLQYRYDY (= SEQ ID Nº 3); (ii): CDR1: SYAMG (= SEQ ID Nº 4), CDR2: AIRRSGRRTYYADSVKG (= SEQ ID Nº 5), CDR3: ARRVRSSTRYNTGTWWWEY (= SEQ ID Nº 6); (iii): CDR1: RYTMG (= SEQ ID Nº 7), CDR2: AIVRSGGSTYYADSVKG (= SEQ ID Nº 8), CDR3: DRRGRGENYILLYSSGRYEY (= SEQ ID Nº 9), y un segundo dominio variable de inmunoglobulina seleccionado del grupo de dominios variables únicos de inmunoglobulina (iv) y (v) definidos por comprender las siguientes secuencias de CDR: (iv): CDR1: SYAMG (= SEQ ID Nº 10), CDR2: AISWSGGSTYYADSVKG (= SEQ ID Nº 11), CDR3: SPIPYGSLLRRRNNYDY (= SEQ ID Nº 12); (v): CDR1: SYAMG (= SEQ ID Nº 13), CDR2: AISWRSGSTYYADSVKG (= SEQ ID Nº 14), CDR3: DPRGYGVAYVSAYYEY (= SEQ ID Nº 15).
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15197999 | 2015-12-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR106949A1 true AR106949A1 (es) | 2018-03-07 |
Family
ID=54782606
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP160103720A AR106949A1 (es) | 2015-12-04 | 2016-12-02 | Polipéptidos biparatópicos que antagonizan la señalización wnt en células tumorales |
Country Status (32)
| Country | Link |
|---|---|
| US (2) | US10597449B2 (es) |
| EP (2) | EP3383425B1 (es) |
| JP (2) | JP6728355B2 (es) |
| KR (1) | KR102802241B1 (es) |
| CN (1) | CN108289943B (es) |
| AR (1) | AR106949A1 (es) |
| AU (1) | AU2016363787B2 (es) |
| BR (1) | BR112018010537A2 (es) |
| CL (1) | CL2018001384A1 (es) |
| CO (1) | CO2018005680A2 (es) |
| CY (1) | CY1123454T1 (es) |
| DK (1) | DK3383425T3 (es) |
| EA (1) | EA201891331A1 (es) |
| ES (1) | ES2821099T3 (es) |
| HR (1) | HRP20201528T1 (es) |
| HU (1) | HUE051777T2 (es) |
| IL (1) | IL259119B (es) |
| LT (1) | LT3383425T (es) |
| MA (2) | MA54648A (es) |
| MX (1) | MX380414B (es) |
| MY (1) | MY200933A (es) |
| PE (1) | PE20181515A1 (es) |
| PH (1) | PH12018501155B1 (es) |
| PL (1) | PL3383425T3 (es) |
| PT (1) | PT3383425T (es) |
| RS (1) | RS60823B1 (es) |
| SA (1) | SA518391728B1 (es) |
| SG (1) | SG11201804510PA (es) |
| SI (1) | SI3383425T1 (es) |
| TW (1) | TWI734719B (es) |
| UA (1) | UA122079C2 (es) |
| WO (1) | WO2017093478A1 (es) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2017120287A (ru) | 2012-02-28 | 2018-11-15 | АйАрЭм ЭлЭлСи | ОТБОР БОЛЬНЫХ РАКОМ ДЛЯ ВВЕДЕНИЯ ИНГИБИТОРОВ СИГНАЛЬНОГО ПУТИ Wnt НА ОСНОВАНИИ СТАТУСА МУТАЦИИ RNF43 |
| IL300122A (en) | 2015-11-18 | 2023-03-01 | Merck Sharp ַ& Dohme Llc | Substances that bind to PD1 and/or LAG3 |
| HRP20201528T1 (hr) * | 2015-12-04 | 2020-12-11 | Boehringer Ingelheim International Gmbh | Biparatopikalni polipeptidi koji antagoniziraju wnt signalizaciju u tumorskim stanicama |
| TWI794171B (zh) | 2016-05-11 | 2023-03-01 | 美商滬亞生物國際有限公司 | Ｈｄａｃ抑制劑與ｐｄ-ｌ１抑制劑之組合治療 |
| TWI808055B (zh) | 2016-05-11 | 2023-07-11 | 美商滬亞生物國際有限公司 | Hdac 抑制劑與 pd-1 抑制劑之組合治療 |
| KR102717656B1 (ko) * | 2017-05-31 | 2024-10-14 | 베링거 인겔하임 인터내셔날 게엠베하 | 종양 세포에서 wnt 신호 전달을 길항하는 폴리펩티드 |
| GB2597623A (en) | 2017-08-07 | 2022-02-02 | Univ California | Platform for generating safe cell therapeutics |
| MX2020005424A (es) | 2017-11-29 | 2020-12-03 | Univ Texas | Composiciones y metodos para terapia contra el cancer. |
| EP3732201A4 (en) | 2017-12-19 | 2022-04-20 | Surrozen Operating, Inc. | WNT SURROGATES AND THEIR USES |
| EP3820906B1 (en) * | 2018-07-05 | 2025-10-15 | Surrozen Operating, Inc. | Multi-specific wnt surrogate molecules and uses thereof |
| WO2020080941A1 (en) * | 2018-10-16 | 2020-04-23 | Umc Utrecht Holding B.V. | Anti- low-density lipoprotein receptor-related protein 5/6 antibodies |
| CN113646048A (zh) | 2019-03-29 | 2021-11-12 | 勃林格殷格翰国际有限公司 | 抗癌组合疗法 |
| EP3947455A1 (en) | 2019-03-29 | 2022-02-09 | Boehringer Ingelheim International GmbH | Anticancer combination therapy |
| CN121021694A (zh) | 2019-05-04 | 2025-11-28 | 印希比生物科学有限公司 | 结合cd123的多肽及其用途 |
| JP2022531718A (ja) * | 2019-05-08 | 2022-07-08 | ２セブンティ バイオ インコーポレイテッド | Ｃｄ１２３標的免疫療法 |
| MX2022001947A (es) * | 2019-08-14 | 2022-06-14 | Modmab Therapeutics Inc | Anticuerpos que se unen a las proteinas lrp5 y metodos de uso. |
| US20220281969A1 (en) * | 2019-08-14 | 2022-09-08 | Modmab Therapeutics Inc. | Antibodies that bind to lrp6 proteins and methods of use |
| WO2021061842A1 (en) | 2019-09-23 | 2021-04-01 | Twist Bioscience Corporation | Variant nucleic acid libraries for single domain antibodies |
| CN112794914B (zh) * | 2019-11-14 | 2022-09-16 | 深圳华大生命科学研究院 | 一种基于噬菌体展示技术开发的alk纳米抗体及其应用 |
| WO2021163490A1 (en) * | 2020-02-14 | 2021-08-19 | University Of Washington | Targeted depletion of bacteria from mixed populations through programmable cell-cell adhesion |
| WO2022204316A2 (en) * | 2021-03-24 | 2022-09-29 | Twist Bioscience Corporation | Variant nucleic acid libraries for cd3 |
| EP4372006A4 (en) * | 2021-07-16 | 2025-10-08 | Brightpath Biotherapeutics Co Ltd | ANTIBODY OR ANTIBODY DERIVATIVE TO TIM-3 ANTIGEN, AND USE THEREOF |
| EP4646436A2 (en) * | 2023-01-05 | 2025-11-12 | Harpoon Therapeutics, Inc. | Trop2 targeting trispecific protein for treatment of cancer |
| CN116375851B (zh) * | 2023-03-03 | 2024-03-22 | 中国农业科学院兰州兽医研究所 | 一种抗禽流感病毒np蛋白的纳米抗体及其制备方法与应用 |
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| EP0739981A1 (en) | 1995-04-25 | 1996-10-30 | Vrije Universiteit Brussel | Variable fragments of immunoglobulins - use for therapeutic or veterinary purposes |
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| US6528054B1 (en) * | 1998-12-28 | 2003-03-04 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of breast cancer |
| ES2529300T3 (es) | 2000-04-12 | 2015-02-18 | Novozymes Biopharma Dk A/S | Proteínas de fusión de albúmina |
| ATE477280T1 (de) | 2001-06-28 | 2010-08-15 | Domantis Ltd | Doppelspezifischer ligand und dessen verwendung |
| WO2003059934A2 (en) | 2001-12-21 | 2003-07-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| AU2003283137B8 (en) | 2002-11-08 | 2010-07-29 | Ablynx N.V. | Camelidae antibodies against immunoglobulin E and use thereof for the treatment of allergic disorders |
| KR20070084170A (ko) | 2004-10-13 | 2007-08-24 | 아블린쓰 엔.브이. | 알쯔하이머병 등의 퇴행성 신경 질환의 치료 및 진단을위한 단일 도메인 카멜리드 항-아밀로이드 베타 항체 및이를 포함하는 폴리펩타이드 |
| LT2949668T (lt) | 2005-05-18 | 2019-11-11 | Ablynx Nv | Pagerinti nanokūnai tm prieš navikų nekrozės faktorių alfa |
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| SG185415A1 (en) * | 2010-05-06 | 2012-12-28 | Novartis Ag | Compositions and methods of use for therapeutic low density lipoprotein - related protein 6 (lrp6) multivalent antibodies |
| WO2011138392A1 (en) | 2010-05-06 | 2011-11-10 | Novartis Ag | Compositions and methods of use for therapeutic low density lipoprotein -related protein 6 (lrp6) antibodies |
| CA2812785A1 (en) * | 2010-10-20 | 2012-04-26 | Genentech, Inc. | Methods and compositions for modulating the wnt pathway |
| US9527925B2 (en) | 2011-04-01 | 2016-12-27 | Boehringer Ingelheim International Gmbh | Bispecific binding molecules binding to VEGF and ANG2 |
| US8790650B2 (en) * | 2011-04-28 | 2014-07-29 | Vanderbilt University | Methods of using an antibody to inhibit WNT-mediated cardiac remodeling |
| PH12013502669B1 (en) | 2011-06-23 | 2018-08-10 | Ablynx Nv | Techniques for predicting, detecting and reducing aspecific protein interference in assays involving immunoglobulin single variable domains |
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| EP2888279A1 (en) * | 2012-08-22 | 2015-07-01 | Glaxo Group Limited | Anti lrp6 antibodies |
| HRP20201528T1 (hr) * | 2015-12-04 | 2020-12-11 | Boehringer Ingelheim International Gmbh | Biparatopikalni polipeptidi koji antagoniziraju wnt signalizaciju u tumorskim stanicama |
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