NZ705606A - Methods for identifying antibodies with reduced immunogenicity - Google Patents
Methods for identifying antibodies with reduced immunogenicityInfo
- Publication number
- NZ705606A NZ705606A NZ705606A NZ70560613A NZ705606A NZ 705606 A NZ705606 A NZ 705606A NZ 705606 A NZ705606 A NZ 705606A NZ 70560613 A NZ70560613 A NZ 70560613A NZ 705606 A NZ705606 A NZ 705606A
- Authority
- NZ
- New Zealand
- Prior art keywords
- reduced immunogenicity
- methods
- identifying antibodies
- antibody
- identifying
- Prior art date
Links
- 230000005847 immunogenicity Effects 0.000 title abstract 3
Classifications
-
- 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
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/241—Tumor Necrosis Factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P17/06—Antipsoriatics
-
- 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
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
- C07K16/4208—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an idiotypic determinant on Ig
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
- C40B40/10—Libraries containing peptides or polypeptides, or derivatives thereof
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/525—Tumor necrosis factor [TNF]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/10—Screening for compounds of potential therapeutic value involving cells
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261703170P | 2012-09-19 | 2012-09-19 | |
| PCT/US2013/060480 WO2014047222A2 (en) | 2012-09-19 | 2013-09-18 | Methods for identifying antibodies with reduced immunogenicity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ705606A true NZ705606A (en) | 2018-05-25 |
Family
ID=49304336
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ705606A NZ705606A (en) | 2012-09-19 | 2013-09-18 | Methods for identifying antibodies with reduced immunogenicity |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US9279016B2 (forum.php) |
| EP (2) | EP3211006A3 (forum.php) |
| JP (1) | JP2015537190A (forum.php) |
| KR (1) | KR20150056788A (forum.php) |
| CN (1) | CN104704000A (forum.php) |
| AU (1) | AU2013318147B2 (forum.php) |
| BR (1) | BR112015005857A2 (forum.php) |
| CA (1) | CA2885422A1 (forum.php) |
| CY (1) | CY1118893T1 (forum.php) |
| DK (1) | DK2897978T3 (forum.php) |
| ES (1) | ES2621285T3 (forum.php) |
| HR (1) | HRP20170937T1 (forum.php) |
| HU (1) | HUE032569T2 (forum.php) |
| IL (1) | IL237833A0 (forum.php) |
| IN (1) | IN2015DN01967A (forum.php) |
| LT (1) | LT2897978T (forum.php) |
| MX (1) | MX2015003541A (forum.php) |
| NZ (1) | NZ705606A (forum.php) |
| PL (1) | PL2897978T3 (forum.php) |
| PT (1) | PT2897978T (forum.php) |
| RS (1) | RS56093B1 (forum.php) |
| RU (1) | RU2648141C2 (forum.php) |
| SG (1) | SG11201502094TA (forum.php) |
| SI (1) | SI2897978T1 (forum.php) |
| SM (1) | SMT201700255T1 (forum.php) |
| TW (1) | TWI519646B (forum.php) |
| WO (1) | WO2014047222A2 (forum.php) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106478802B (zh) * | 2016-10-11 | 2019-08-09 | 浙江省人民医院 | TNF-α蛋白B细胞表位，含此表位的多抗原肽及应用 |
| EP3558363A1 (en) | 2016-12-21 | 2019-10-30 | Amgen Inc. | Anti-tnf alpha antibody formulations |
| EP3592851B1 (en) * | 2017-03-07 | 2024-11-27 | F. Hoffmann-La Roche AG | Method for discovery of alternative antigen specific antibody variants |
| TW202039554A (zh) * | 2018-12-19 | 2020-11-01 | 瑞士商諾華公司 | 抗ＴＮＦ－α抗體 |
| CA3143478A1 (en) * | 2019-07-09 | 2021-01-14 | Tomer Hertz | Antibodies with reduced immunogenicity |
| JP2022550390A (ja) | 2019-09-30 | 2022-12-01 | スキロム ゲゼルシャフト ミット ベシュレンクテル ハフツング | ｉＲｈｏｍ２エピトープに結合するタンパク質バインダー |
| FR3104582A1 (fr) * | 2019-12-17 | 2021-06-18 | Commissariat A L'energie Atomique Et Aux Energies Alternatives | Variants de l’adalimumab au potentiel immunogène réduit |
| CN113125714B (zh) * | 2019-12-31 | 2023-06-16 | 科美博阳诊断技术(上海)有限公司 | 一种人类免疫缺陷病毒抗体检测试剂盒及其应用 |
| WO2021147642A1 (en) * | 2020-01-20 | 2021-07-29 | Bio-Thera Solutions, Ltd. | Methods, models and systems related to antibody immunogenicity |
| KR102568430B1 (ko) * | 2020-11-16 | 2023-08-24 | 바디텍메드(주) | 항 약물 항체의 신속 검출 방법 |
| WO2022184594A1 (en) | 2021-03-01 | 2022-09-09 | Scirhom Gmbh | Humanized antibodies against irhom2 |
| CA3213771A1 (en) | 2021-03-29 | 2022-10-06 | Scirhom Gmbh | Methods of treatment using protein binders to irhom2 epitopes |
| WO2022214664A1 (en) | 2021-04-09 | 2022-10-13 | Philogen S.P.A. | Improved interferon-gamma mutant |
| WO2024023246A1 (en) | 2022-07-28 | 2024-02-01 | Philogen S.P.A. | Antibody binding to pd1 |
| WO2024033362A1 (en) | 2022-08-08 | 2024-02-15 | Atb Therapeutics | Humanized antibodies against cd79b |
| WO2025180665A1 (en) | 2024-02-28 | 2025-09-04 | Evotec International Gmbh | Antibodies binding to cd2, and multifunctional molecules comprising such antibodies |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| DE3687170T2 (de) | 1985-01-25 | 1993-04-01 | Kitasato Inst | Antitumorale antibiotika und deren herstellung. |
| US5264357A (en) | 1985-05-24 | 1993-11-23 | Genentech, Inc. | Nucleic acids vectors and cells for the synthesis of membrane anchor fusion polypeptides |
| US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| US5264586A (en) | 1991-07-17 | 1993-11-23 | The Scripps Research Institute | Analogs of calicheamicin gamma1I, method of making and using the same |
| US5635483A (en) | 1992-12-03 | 1997-06-03 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Tumor inhibiting tetrapeptide bearing modified phenethyl amides |
| US5780588A (en) | 1993-01-26 | 1998-07-14 | Arizona Board Of Regents | Elucidation and synthesis of selected pentapeptides |
| US5773001A (en) | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
| US5712374A (en) | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
| US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
| US6090382A (en) | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
| CZ292465B6 (cs) * | 1996-02-09 | 2003-09-17 | Abbott Laboratories (Bermuda) Ltd. | Lidské protilátky k lidskému TNFalfa |
| US5834597A (en) | 1996-05-20 | 1998-11-10 | Protein Design Labs, Inc. | Mutated nonactivating IgG2 domains and anti CD3 antibodies incorporating the same |
| US6787308B2 (en) | 1998-07-30 | 2004-09-07 | Solexa Ltd. | Arrayed biomolecules and their use in sequencing |
| AR021833A1 (es) | 1998-09-30 | 2002-08-07 | Applied Research Systems | Metodos de amplificacion y secuenciacion de acido nucleico |
| CA2347833A1 (en) | 1998-11-18 | 2000-05-25 | Genentech, Inc. | Antibody variants with higher binding affinity compared to parent antibodies |
| US7211390B2 (en) | 1999-09-16 | 2007-05-01 | 454 Life Sciences Corporation | Method of sequencing a nucleic acid |
| EP1218543A2 (en) | 1999-09-29 | 2002-07-03 | Solexa Ltd. | Polynucleotide sequencing |
| US6686168B1 (en) | 1999-11-04 | 2004-02-03 | Zymogenetics, Inc. | Cell surface display of proteins by recombinant host cells |
| UA81743C2 (uk) * | 2000-08-07 | 2008-02-11 | Центокор, Инк. | МОНОКЛОНАЛЬНЕ АНТИТІЛО ЛЮДИНИ, ЩО СПЕЦИФІЧНО ЗВ'ЯЗУЄТЬСЯ З ФАКТОРОМ НЕКРОЗУ ПУХЛИН АЛЬФА (ФНПα), ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ, ЩО ЙОГО МІСТИТЬ, ТА СПОСІБ ЛІКУВАННЯ РЕВМАТОЇДНОГО АРТРИТУ |
| AU2001293163A1 (en) | 2000-09-27 | 2002-04-08 | Lynx Therapeutics, Inc. | Method for determining relative abundance of nucleic acid sequences |
| US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
| US6956114B2 (en) | 2001-10-30 | 2005-10-18 | '454 Corporation | Sulfurylase-luciferase fusion proteins and thermostable sulfurylase |
| US7057026B2 (en) | 2001-12-04 | 2006-06-06 | Solexa Limited | Labelled nucleotides |
| US20030206898A1 (en) | 2002-04-26 | 2003-11-06 | Steven Fischkoff | Use of anti-TNFalpha antibodies and another drug |
| US20040115814A1 (en) | 2002-09-30 | 2004-06-17 | Protein Design Labs, Inc. | Efficient generation of stable expression cell lines through the use of scorable homeostatic reporter genes |
| NZ547633A (en) | 2003-11-06 | 2010-08-27 | Seattle Genetics Inc | Monomethylvaline compounds capable of conjugation to ligands |
| WO2005123780A2 (en) | 2004-04-09 | 2005-12-29 | Protein Design Labs, Inc. | Alteration of fcrn binding affinities or serum half-lives of antibodies by mutagenesis |
| TWI439284B (zh) * | 2004-04-09 | 2014-06-01 | Abbvie Biotechnology Ltd | 用於治療ＴＮＦα相關失調症之多重可變劑量療法 |
| US7632497B2 (en) | 2004-11-10 | 2009-12-15 | Macrogenics, Inc. | Engineering Fc Antibody regions to confer effector function |
| CA2629095A1 (en) | 2005-11-12 | 2007-05-24 | Eli Lily And Company | Anti-egfr antibodies |
| JP5759722B2 (ja) | 2007-08-28 | 2015-08-05 | アッヴィ バイオテクノロジー リミテッド | アダリムマブの結合蛋白質を含む組成物及び方法 |
| WO2009059235A2 (en) | 2007-11-01 | 2009-05-07 | Facet Biotech Corporation | Immunoglobulin display vectors |
| CA2758964A1 (en) * | 2009-04-16 | 2010-10-21 | Abbott Biotherapeutics Corp. | Anti-tnf-.alpha. antibodies and their uses |
| GB0909904D0 (en) * | 2009-06-09 | 2009-07-22 | Affitech As | Product |
| PE20130393A1 (es) * | 2010-03-11 | 2013-04-07 | Rinat Neuroscience Corp | Anticuerpos con union de antigenos dependiente de ph |
| BR112013002444A2 (pt) * | 2010-08-13 | 2016-05-24 | Roche Glycart Ag | anticorpo, polinucleotídeo e polipeotídeo isolados, composição, vetor, cécula hospedeira, conjulgado de anticorpo, formulação farmacêutica, uso do anticorpo, métodos para produzir um anticorpo, tratar um indivíduo, induzir a lise celular de uma célula tumorosa e diagnosticar uma doença em um indivíduo |
| NZ610091A (en) * | 2010-10-20 | 2015-02-27 | Oxford Biotherapeutics Ltd | Antibodies |
-
2013
- 2013-09-18 JP JP2015533163A patent/JP2015537190A/ja active Pending
- 2013-09-18 WO PCT/US2013/060480 patent/WO2014047222A2/en active Application Filing
- 2013-09-18 NZ NZ705606A patent/NZ705606A/en not_active IP Right Cessation
- 2013-09-18 EP EP17154662.5A patent/EP3211006A3/en not_active Withdrawn
- 2013-09-18 CA CA2885422A patent/CA2885422A1/en not_active Abandoned
- 2013-09-18 PT PT137734745T patent/PT2897978T/pt unknown
- 2013-09-18 TW TW102134040A patent/TWI519646B/zh not_active IP Right Cessation
- 2013-09-18 BR BR112015005857A patent/BR112015005857A2/pt active Search and Examination
- 2013-09-18 PL PL13773474T patent/PL2897978T3/pl unknown
- 2013-09-18 EP EP13773474.5A patent/EP2897978B1/en active Active
- 2013-09-18 SG SG11201502094TA patent/SG11201502094TA/en unknown
- 2013-09-18 HR HRP20170937TT patent/HRP20170937T1/hr unknown
- 2013-09-18 LT LTEP13773474.5T patent/LT2897978T/lt unknown
- 2013-09-18 CN CN201380048863.XA patent/CN104704000A/zh active Pending
- 2013-09-18 MX MX2015003541A patent/MX2015003541A/es unknown
- 2013-09-18 IN IN1967DEN2015 patent/IN2015DN01967A/en unknown
- 2013-09-18 DK DK13773474.5T patent/DK2897978T3/en active
- 2013-09-18 RU RU2015111671A patent/RU2648141C2/ru not_active IP Right Cessation
- 2013-09-18 US US14/030,977 patent/US9279016B2/en not_active Expired - Fee Related
- 2013-09-18 ES ES13773474.5T patent/ES2621285T3/es active Active
- 2013-09-18 AU AU2013318147A patent/AU2013318147B2/en not_active Ceased
- 2013-09-18 RS RS20170609A patent/RS56093B1/sr unknown
- 2013-09-18 SM SM20170255T patent/SMT201700255T1/it unknown
- 2013-09-18 KR KR1020157007286A patent/KR20150056788A/ko not_active Withdrawn
- 2013-09-18 HU HUE13773474A patent/HUE032569T2/en unknown
- 2013-09-18 SI SI201330608A patent/SI2897978T1/sl unknown
-
2015
- 2015-03-19 IL IL237833A patent/IL237833A0/en unknown
-
2017
- 2017-04-11 CY CY20171100428T patent/CY1118893T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NZ705606A (en) | Methods for identifying antibodies with reduced immunogenicity | |
| IL271697A (en) | Antibodies against CXCR3 | |
| PH12014501427B1 (en) | Anti-phf-tau antibodies and their uses | |
| CO7151521A2 (es) | Anticuerpos anti-fcrn | |
| EP2722343A4 (en) | ANTI-ERBB3 ANTIBODIES | |
| UY34456A (es) | Anticuerpos anti-il-36r | |
| IL228001B (en) | Antibodies to 70cd | |
| GB201103955D0 (en) | Antibodies | |
| GB201103836D0 (en) | Conjugation process | |
| AU2013316100A1 (en) | Antibody evolution immunogens | |
| MX370649B (es) | Proceso para la preparacion de teneligliptina. | |
| WO2014033158A3 (en) | Pcsk9 peptide vaccine | |
| EP2847227A4 (en) | ANTI-ERBB2 ANTIBODY VARIANTS | |
| EP2804876A4 (en) | NEW ANTIBODIES | |
| ZA201502210B (en) | Methods for identifying hiv neutralizing antibodies | |
| EP2714074A4 (en) | ANTIBODIES AGAINST EMR1 | |
| UA71014U (ru) | Способ экспрессной оценки эффективности вакцинации | |
| UA72478U (ru) | Применение полентара как средства фригопротекторного действия | |
| GB201209584D0 (en) | Modified antibodies | |
| GB201102806D0 (en) | Fuel economy patent abstract |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PSEA | Patent sealed | ||
| LAPS | Patent lapsed |