PE20080911A1 - Anticuerpo anti-vegf - Google Patents

Anticuerpo anti-vegf

Info

Publication number
PE20080911A1
PE20080911A1 PE2007001129A PE2007001129A PE20080911A1 PE 20080911 A1 PE20080911 A1 PE 20080911A1 PE 2007001129 A PE2007001129 A PE 2007001129A PE 2007001129 A PE2007001129 A PE 2007001129A PE 20080911 A1 PE20080911 A1 PE 20080911A1
Authority
PE
Peru
Prior art keywords
antibody
vegf antibody
her2
treated
vegf
Prior art date
Application number
PE2007001129A
Other languages
English (en)
Spanish (es)
Inventor
Thomas Friess
Max Hasmann
Werner Scheuer
Original Assignee
Hoffmann La Roche
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=37607207&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=PE20080911(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of PE20080911A1 publication Critical patent/PE20080911A1/es

Links

Classifications

    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • 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
    • C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • C07K2317/70—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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Mycology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Endocrinology (AREA)
  • Oncology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
PE2007001129A 2006-08-21 2007-08-20 Anticuerpo anti-vegf PE20080911A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP06017330 2006-08-21

Publications (1)

Publication Number Publication Date
PE20080911A1 true PE20080911A1 (es) 2008-08-15

Family

ID=37607207

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2007001129A PE20080911A1 (es) 2006-08-21 2007-08-20 Anticuerpo anti-vegf

Country Status (28)

Country Link
US (6) US20080050385A1 (enExample)
EP (2) EP2056874B1 (enExample)
JP (3) JP2010501498A (enExample)
KR (1) KR101136763B1 (enExample)
CN (1) CN101505792B (enExample)
AR (1) AR062419A1 (enExample)
AU (1) AU2007287794B2 (enExample)
BR (1) BRPI0715829A2 (enExample)
CA (1) CA2660681A1 (enExample)
CL (1) CL2007002404A1 (enExample)
CO (1) CO6150193A2 (enExample)
CR (1) CR10590A (enExample)
DK (1) DK2056874T3 (enExample)
ES (2) ES2392630T3 (enExample)
IL (2) IL196810A0 (enExample)
MA (1) MA30654B1 (enExample)
MX (1) MX2009001715A (enExample)
MY (1) MY150756A (enExample)
NO (1) NO20090450L (enExample)
NZ (1) NZ574580A (enExample)
PE (1) PE20080911A1 (enExample)
PL (1) PL2056874T3 (enExample)
RU (1) RU2528884C2 (enExample)
SG (1) SG174090A1 (enExample)
SI (1) SI2056874T1 (enExample)
TW (2) TW201107346A (enExample)
WO (1) WO2008022746A1 (enExample)
ZA (1) ZA200901200B (enExample)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MXPA02011379A (es) * 2000-05-19 2003-06-06 Genentech Inc Ensayo de deteccion de genes para mejorar la probabilidad de una respuesta efectiva a terapia de cancer con el antagonista erbb.
KR20190126461A (ko) 2004-07-22 2019-11-11 제넨테크, 인크. Ｈｅｒ２ 항체 조성물
JO3000B1 (ar) * 2004-10-20 2016-09-05 Genentech Inc مركبات أجسام مضادة .
CN101115849A (zh) * 2004-12-07 2008-01-30 健泰科生物技术公司 选择her抑制剂疗法的患者
KR20200058588A (ko) 2005-01-21 2020-05-27 제넨테크, 인크. Ｈｅｒ 항체의 고정 용량 투여법
MY152164A (en) 2005-02-23 2014-08-15 Genentech Inc Extending time to disease progression or survival in cancer patients
PE20070207A1 (es) * 2005-07-22 2007-03-09 Genentech Inc Tratamiento combinado de los tumores que expresan el her
DK2056874T3 (da) * 2006-08-21 2012-10-15 Hoffmann La Roche Tumorterapi med et anti-vegf-antistof
KR20150039212A (ko) 2007-03-02 2015-04-09 제넨테크, 인크. 낮은 ｈｅｒ３ 발현을 기초로 한 ｈｅｒ 이량체화 억제제에 대한 반응 예측
TWI472339B (zh) 2008-01-30 2015-02-11 Genentech Inc 包含結合至ｈｅｒ２結構域ii之抗體及其酸性變異體的組合物
BRPI0812682A2 (pt) 2008-06-16 2010-06-22 Genentech Inc tratamento de cáncer de mama metastático
CN103153339B (zh) 2010-05-27 2021-05-04 根马布股份公司 针对her2表位的单克隆抗体
NZ604003A (en) 2010-05-27 2015-04-24 Genmab As Monoclonal antibodies against her2
CA2804348A1 (en) * 2010-07-19 2012-01-26 F. Hoffmann-La Roche Ag Blood plasma biomarkers for bevacizumab combination therapies for treatment of pancreatic cancer
MY162825A (en) * 2010-08-20 2017-07-31 Novartis Ag Antibodies for epidermal growth factor receptor 3 (her3)
AU2012245116A1 (en) 2011-04-20 2013-11-07 Genmab A/S Bispecific antibodies against HER2 and CD3
BR112014007521A8 (pt) 2011-10-14 2018-04-10 Genentech Inc método para estender a sobrevida livre de progressão em uma população com câncer de mama, artigo de fabricação, método para produção de um artigo de fabricação, para garantir o uso seguro e efetivo de pertuzumabe, de tratar câncer de mama, bolsa intravenosa, método de tratar câncer gástrico, de tratar adenocarcinoma do estômago e de melhora de sobrevida
AU2012348600A1 (en) * 2011-12-05 2014-05-22 F. Hoffmann-La Roche Ag Blood plasma biomarkers for bevacizumab combination therapies for treatment of breast cancer
US20150147340A1 (en) * 2012-03-30 2015-05-28 Fibrogen, Inc. Therapeutic methods for peritoneal carcinomatosis
EA201591643A1 (ru) 2013-04-16 2016-02-29 Дженентек, Инк. Варианты пертузумаба и их аналитическая характеристика
KR20160141857A (ko) 2014-04-25 2016-12-09 제넨테크, 인크. 트라스투주맙-mcc-dm1 및 퍼투주맙을 이용하는 초기 유방암의 치료방법
TW201619200A (zh) * 2014-10-10 2016-06-01 麥迪紐有限責任公司 人類化抗－ｏｘ４０抗體及其用途
HUE068105T2 (hu) 2015-05-30 2024-12-28 Hoffmann La Roche Eljárások korábban kezeletlen her2-pozitív metasztatikus emlõrák kezelésére
WO2017087280A1 (en) 2015-11-16 2017-05-26 Genentech, Inc. Methods of treating her2-positive cancer
CN106729743B (zh) * 2015-11-23 2021-09-21 四川科伦博泰生物医药股份有限公司 抗ErbB2抗体-药物偶联物及其组合物、制备方法和应用
TW202140776A (zh) * 2016-04-26 2021-11-01 美商美國泰福生技股份有限公司 細胞培養基
KR102313262B1 (ko) 2016-12-28 2021-10-14 제넨테크, 인크. 진행성 her2 발현 암의 치료
US10849849B2 (en) 2017-01-17 2020-12-01 Genentech Inc. Subcutaneous HER2 antibody formulations
ES2969041T3 (es) 2017-03-02 2024-05-16 Genentech Inc Tratamiento adyuvante del cáncer de mama positivo para HER2
AU2018258263A1 (en) 2017-04-24 2019-10-24 Genentech, Inc. ErbB2/Her2 mutations in the transmembrane or juxtamembrane domain
MX2022015884A (es) 2020-06-29 2023-04-03 Genentech Inc Combinacion de dosis fija de pertuzumab mas trastuzumab.
WO2022051721A1 (en) * 2020-09-04 2022-03-10 The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Combination compositions and methods for treating cancer

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989006692A1 (en) 1988-01-12 1989-07-27 Genentech, Inc. Method of treating tumor cells by inhibiting growth factor receptor function
WO1994004679A1 (en) 1991-06-14 1994-03-03 Genentech, Inc. Method for making humanized antibodies
DE122004000008I1 (de) 1991-06-14 2005-06-09 Genentech Inc Humanisierter Heregulin Antikörper.
DK1167384T3 (da) 1992-10-28 2007-04-10 Genentech Inc Vaskular endotheliel cellevækstfaktor antagonister
EP0907649A1 (en) 1996-06-27 1999-04-14 Pfizer Inc. Derivatives of 2-(2-oxo-ethylidene)-imidazolidin-4-one and their use as farnesyl protein transferase inhibitors
CN100415772C (zh) 1996-10-18 2008-09-03 基因技术股份有限公司 抗ErbB2抗体
US20020032315A1 (en) 1997-08-06 2002-03-14 Manuel Baca Anti-vegf antibodies
US6884879B1 (en) * 1997-04-07 2005-04-26 Genentech, Inc. Anti-VEGF antibodies
PT1695985E (pt) 1997-04-07 2011-06-06 Genentech Inc Métodos para formar anticorpos humanizados por mutagénese aleatória
DK1325932T5 (da) 1997-04-07 2005-10-03 Genentech Inc Anti-VEGF antistoffer
ZA9811162B (en) 1997-12-12 2000-06-07 Genentech Inc Treatment with anti-ERBB2 antibodies.
JPH11236333A (ja) 1997-12-30 1999-08-31 Pfizer Prod Inc 抗ガン剤として有用なイミダゾリン−４−オン誘導体
AU4079999A (en) 1998-05-15 1999-12-06 Imclone Systems Incorporated Treatment of human tumors with radiation and inhibitors of growth factor receptor tyrosine kinases
GEP20033001B (en) 1998-08-27 2003-06-25 Pfizer Prod Inc Alkynyl-Substituted Quinolin-2-One Derivatives Useful As Anticancer Agents
JP3494409B2 (ja) 1998-08-27 2004-02-09 ファイザー・プロダクツ・インク 抗がん剤として有用なアルキニル置換キノリン−２−オン誘導体
EP1135498B1 (en) 1998-11-18 2008-01-23 Genentech, Inc. Antibody variants with higher binding affinity compared to parent antibodies
EP1006113A1 (en) 1998-12-02 2000-06-07 Pfizer Products Inc. Derivatives of 2-(2-oxo-ethylidene)-imidazolidin-4-one and their use to inhibit abnormal cell growth
AU1687500A (en) 1998-12-16 2000-07-03 Kyowa Hakko Kogyo Co. Ltd. Antihuman vegf monoclonal antibody
JP4090200B2 (ja) 1999-02-11 2008-05-28 ファイザー・プロダクツ・インク 抗癌薬として有用なヘテロアリール置換キノリン−２−オン誘導体
US6586447B1 (en) 1999-04-01 2003-07-01 Pfizer Inc 3,3-disubstituted-oxindole derivatives useful as anticancer agents
ES2320311T3 (es) 1999-05-14 2009-05-21 Genentech, Inc. Tratamiento con anticuerpos anti-erbb2.
EP1189634B1 (en) 1999-06-25 2007-02-28 Genentech, Inc. Treating prostate cancer with anti-erbb2 antibodies
US6949245B1 (en) * 1999-06-25 2005-09-27 Genentech, Inc. Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies
MXPA01013458A (es) 1999-06-25 2002-07-30 Genentech Inc Anticuerpos humanizados anti-erbb2 y tratamiento con anticuerpos anti-erbb2.
EP1106612B1 (en) 1999-11-30 2004-02-11 Pfizer Products Inc. Quinoline derivatives useful for inhibiting farnesyl protein transferase
UA75055C2 (uk) 1999-11-30 2006-03-15 Пфайзер Продактс Інк. Похідні бензоімідазолу, що використовуються як антипроліферативний засіб, фармацевтична композиція на їх основі
HN2000000266A (es) 2000-01-21 2001-05-21 Pfizer Prod Inc Compuesto anticanceroso y metodo de separacion de enantiomeros util para sintetizar dicho compuesto.
WO2003042402A2 (en) * 2001-11-13 2003-05-22 Dana-Farber Cancer Institute, Inc. Agents that modulate immune cell activation and methods of use thereof
AU2003222252A1 (en) 2002-03-12 2003-09-29 The General Hospital Corporation Use of signal transduction inhibitors and combination therapies for the prevention or treatment of cancer and angiogenesis related diseases
JP2005522514A (ja) 2002-04-10 2005-07-28 ジェネンテック・インコーポレーテッド 抗ｈｅｒ２抗体改変体
MXPA05012723A (es) 2003-05-30 2006-02-08 Genentech Inc Tratamiento con anticuerpos anti-vgf.
US20040243207A1 (en) 2003-05-30 2004-12-02 Olson Donald R. Medical implant systems
KR20060069825A (ko) 2003-08-01 2006-06-22 제넨테크, 인크. 제한된 다양성을 갖는 항체 ｃｄｒ 폴리펩티드 서열
US20050106667A1 (en) * 2003-08-01 2005-05-19 Genentech, Inc Binding polypeptides with restricted diversity sequences
ATE554107T1 (de) 2003-12-19 2012-05-15 Genentech Inc Als therapeutika geeignete monovalente antikörperfragmente
JP2008511337A (ja) * 2004-09-02 2008-04-17 ジェネンテック・インコーポレーテッド ヘテロ多量体分子
US20060147451A1 (en) * 2004-10-04 2006-07-06 Genentech, Inc. Modulators of hepatocyte growth factor activator
BRPI0611766A2 (pt) * 2005-06-08 2011-12-20 Dana Farber Cancer Inst Inc métodos e composições para o tratamento de infecções persistentes e cáncer por inibição da rota de morte celular programada
TW200812615A (en) * 2006-03-22 2008-03-16 Hoffmann La Roche Tumor therapy with an antibody for vascular endothelial growth factor and an antibody for human epithelial growth factor receptor type 2
DK2056874T3 (da) * 2006-08-21 2012-10-15 Hoffmann La Roche Tumorterapi med et anti-vegf-antistof
JP2013103182A (ja) * 2011-11-15 2013-05-30 Toray Ind Inc スパイラル型流体分離素子およびその製造方法

Also Published As

Publication number Publication date
ZA200901200B (en) 2013-08-28
BRPI0715829A2 (pt) 2013-07-23
EP2056874A1 (en) 2009-05-13
TW200825106A (en) 2008-06-16
US20100285010A1 (en) 2010-11-11
DK2056874T3 (da) 2012-10-15
JP2015214582A (ja) 2015-12-03
ES2392630T3 (es) 2012-12-12
AU2007287794B2 (en) 2013-03-28
CN101505792A (zh) 2009-08-12
EP2441472B1 (en) 2015-06-10
IL238045A0 (en) 2015-05-31
ES2546066T3 (es) 2015-09-18
NZ574580A (en) 2011-12-22
CL2007002404A1 (es) 2008-04-18
SG174090A1 (en) 2011-09-29
RU2009110102A (ru) 2010-09-27
KR20090032136A (ko) 2009-03-31
EP2441472A1 (en) 2012-04-18
AU2007287794A1 (en) 2008-02-28
PL2056874T3 (pl) 2013-02-28
JP2010501498A (ja) 2010-01-21
CN101505792B (zh) 2012-10-03
NO20090450L (no) 2009-02-27
MX2009001715A (es) 2009-02-25
TW201107346A (en) 2011-03-01
RU2528884C2 (ru) 2014-09-20
US20080050385A1 (en) 2008-02-28
MA30654B1 (fr) 2009-08-03
US20130183292A1 (en) 2013-07-18
AR062419A1 (es) 2008-11-05
CO6150193A2 (es) 2010-04-20
WO2008022746A1 (en) 2008-02-28
SI2056874T1 (sl) 2012-12-31
HK1134441A1 (en) 2010-04-30
IL196810A0 (en) 2011-08-01
US20110223159A1 (en) 2011-09-15
CR10590A (es) 2009-03-20
MY150756A (en) 2014-02-28
CA2660681A1 (en) 2008-02-28
US20180251536A1 (en) 2018-09-06
JP2013163687A (ja) 2013-08-22
KR101136763B1 (ko) 2012-04-24
US20150239969A1 (en) 2015-08-27
EP2056874B1 (en) 2012-09-19

Similar Documents

Publication Publication Date Title
PE20080911A1 (es) Anticuerpo anti-vegf
PE20161327A1 (es) Proteinas de enlace al antigeno il-23 humana
PE20090975A1 (es) Terapia de combinacion de un anticuerpo anti-cd20 de tipo ii con un inhibidor de proteasoma
PE20120902A1 (es) Anticuerpos anti-egfl7 humanizados
AR077595A1 (es) Tratamientos de combinacion
CY1120102T1 (el) Συνθεσεις και μεθοδοι για μειωση τριγλυκεριδιων χωρις αυξηση επιπεδων ldl-c σε ενα υποκειμενο επι ταυτοχρονης θεραπειας στατινης
BR112014026740A2 (pt) anticorpo, composição, métodos para tratar um mamífero e para fornecer um anticorpo com adcc realçada, e, uso de um anticorpo
NZ586754A (en) Composition comprising antibody that binds to domain ii of her2 and acidic variants thereof
PE20150212A1 (es) Anticuerpos anti-trka con propiedades inhibitorias mejoradas y sus derivados
BR112022001291A2 (pt) Amidas heterobicíclicas como inibidores de cd38
JOP20190194A1 (ar) مركبات نيوكليوتيدات ثنائية حلقية لعلاج السرطان
PE20091655A1 (es) Farmaco para el cancer de higado
PE20120899A1 (es) Composiciones y metodos para anticuerpos que se dirigen a la proteina de complemento c3b
PE20140806A1 (es) Anticuerpos anti-factor d humanizados y sus usos
EA201001639A1 (ru) Композиции и способы их получения и применения
NI200900022A (es) Anticuerpo especifico de prlr y usos del mismo
PE20120205A1 (es) Combinaciones antitumorales que contienen anticuerpos que reconocen especificamente cd38 y citarabina
UY33407A (es) Anticuerpos específicos del factor gdf8 humano
CR20140542A (es) Anticuerpos biespecíficos anti-vegf7anti-ang-2 y su utilización en el tratamiento de enfermedades vasculares oculares
CR10444A (es) Anticuerpo humanizado de c-kit
MX386489B (es) Inhibidores de ibat para el tratamiento de enfermedades hepaticas.
AR101740A1 (es) Terapia de combinación y composiciones
UA114712C2 (uk) Моноклональне антитіло, яке імуноспецифічно зв'язується з людським psgl-1, та його застосування
UA105405C2 (ru) Гуманизированное антитело против человеческого il-22ra
CR20120508A (es) PROTEÍNA DE FUSIÓN ROBO1-Fc Y SU UTILIZACIÓN EN EL TRATAMIENTO DE TUMORES

Legal Events

Date Code Title Description
FA Abandonment or withdrawal