RU2756318C2 - Мутеины липокалина 2 человека с аффинностью в отношении глипикана-3 (gpc3) - Google Patents

Мутеины липокалина 2 человека с аффинностью в отношении глипикана-3 (gpc3) Download PDF

Info

Publication number
RU2756318C2
RU2756318C2 RU2017135605A RU2017135605A RU2756318C2 RU 2756318 C2 RU2756318 C2 RU 2756318C2 RU 2017135605 A RU2017135605 A RU 2017135605A RU 2017135605 A RU2017135605 A RU 2017135605A RU 2756318 C2 RU2756318 C2 RU 2756318C2
Authority
RU
Russia
Prior art keywords
ser
arg
tyr
asn
leu
Prior art date
Application number
RU2017135605A
Other languages
English (en)
Russian (ru)
Other versions
RU2017135605A3 (enExample
RU2017135605A (ru
Inventor
Марлон Хиннер
Андреа Аллерсдорфер
Рачида Сихам Бел Айба
Михаэла АЛЁ
Александер Виденман
Габриеле МАЧИНЕР
Мартин Хюльсмейер
Original Assignee
ПИЕРИС ФАРМАСЬЮТИКАЛС ГмбХ
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
Application filed by ПИЕРИС ФАРМАСЬЮТИКАЛС ГмбХ filed Critical ПИЕРИС ФАРМАСЬЮТИКАЛС ГмбХ
Publication of RU2017135605A publication Critical patent/RU2017135605A/ru
Publication of RU2017135605A3 publication Critical patent/RU2017135605A3/ru
Application granted granted Critical
Publication of RU2756318C2 publication Critical patent/RU2756318C2/ru

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/02Peptides of undefined number of amino acids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4725Proteoglycans, e.g. aggreccan
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102Mutagenizing nucleic acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00Preparation of peptides or proteins
    • C12P21/02Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Biophysics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Toxicology (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Physics & Mathematics (AREA)
  • Dermatology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Crystallography & Structural Chemistry (AREA)
RU2017135605A 2015-05-18 2016-05-18 Мутеины липокалина 2 человека с аффинностью в отношении глипикана-3 (gpc3) RU2756318C2 (ru)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP15167922.2 2015-05-18
EP15167922 2015-05-18
PCT/EP2016/061058 WO2016184875A1 (en) 2015-05-18 2016-05-18 Muteins of human lipocalin 2 with affinity for glypican-3 (gpc3)

Publications (3)

Publication Number Publication Date
RU2017135605A RU2017135605A (ru) 2019-06-18
RU2017135605A3 RU2017135605A3 (enExample) 2019-11-13
RU2756318C2 true RU2756318C2 (ru) 2021-09-29

Family

ID=53180583

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2017135605A RU2756318C2 (ru) 2015-05-18 2016-05-18 Мутеины липокалина 2 человека с аффинностью в отношении глипикана-3 (gpc3)

Country Status (13)

Country Link
US (2) US10273275B2 (enExample)
EP (1) EP3298029A1 (enExample)
JP (2) JP6942060B2 (enExample)
KR (1) KR20180008649A (enExample)
CN (2) CN114456252A (enExample)
AU (1) AU2016262838B2 (enExample)
BR (1) BR112017020961A2 (enExample)
CA (1) CA2982034A1 (enExample)
MX (1) MX2017014730A (enExample)
RU (1) RU2756318C2 (enExample)
SG (1) SG11201707872WA (enExample)
WO (1) WO2016184875A1 (enExample)
ZA (1) ZA201706605B (enExample)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2707126C2 (ru) 2009-12-07 2019-11-22 Пирис Аг МУТЕИНЫ ЛИПОКАЛИНА 2 ЧЕЛОВЕКА (Lcn2, hNGAL) С АФФИННОСТЬЮ ДЛЯ ОПРЕДЕЛЕННОЙ МИШЕНИ
US10526384B2 (en) 2012-11-19 2020-01-07 Pieris Pharmaceuticals Gmbh Interleukin-17A-specific and interleukin-23-specific binding polypeptides and uses thereof
WO2015177175A2 (en) 2014-05-22 2015-11-26 Pieris Ag Novel specific-binding polypeptides and uses thereof
JP6839087B2 (ja) 2015-01-28 2021-03-03 ピエリス ファーマシューティカルズ ゲーエムベーハー 血管新生に特異的な新規のタンパク質
JP6783797B2 (ja) 2015-05-04 2020-11-11 ピエリス ファーマシューティカルズ ゲーエムベーハー 抗がん融合ポリペプチド
CN114573680A (zh) 2015-05-04 2022-06-03 皮里斯制药有限公司 Cd137特异性的蛋白
MX2017014730A (es) 2015-05-18 2018-06-28 Pieris Pharmaceuticals Gmbh Muteinas de lipocalina 2 humana con afinidad por glipicano-3 (gpc3).
EP3298030B1 (en) * 2015-05-18 2023-01-18 Pieris Pharmaceuticals GmbH Anti-cancer fusion polypeptide
EP3115371A1 (en) 2015-07-07 2017-01-11 Sanofi Fusion molecules
CN108699162A (zh) 2015-11-30 2018-10-23 皮里斯澳大利亚有限公司 新型抗血管生成融合多肽
TW201725212A (zh) 2015-12-10 2017-07-16 第一三共股份有限公司 特異性於降鈣素基因相關胜肽的新穎蛋白
SG11202106353VA (en) 2019-02-26 2021-07-29 Pieris Pharmaceuticals Gmbh Novel fusion proteins specific for cd137 and gpc3
EP3946417A1 (en) * 2019-03-29 2022-02-09 Pieris Pharmaceuticals GmbH Inhaled administration of lipocalin muteins
EP4161957A1 (en) 2020-06-05 2023-04-12 Pieris Pharmaceuticals GmbH Multimeric immunomodulator targeting 4-1bb

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007107563A2 (en) * 2006-03-20 2007-09-27 Technische Universität München Muteins of tear lipocalin with affinity for the t-cell coreceptor cd4
RU2395519C2 (ru) * 2005-08-09 2010-07-27 Онкотерапи Сайенс, Инк. Глипикан-3 (gpc3)-производные антигенные пептиды, отторгающие опухоли, используемые для нla-a2-положительных пациентов, и фармацевтическая продукция, включающая их
WO2012065978A1 (en) * 2010-11-15 2012-05-24 Pieris Ag Muteins of human lipocalin 2 with affinity for glypican-3 (gpc3)
WO2013174783A1 (en) * 2012-05-23 2013-11-28 Pieris Ag Lipocalin muteins with binding-affinity for glypican-3 (gpc-3) and use of lipocalin muteins for target-specific delivery to cells expressing gpc-3
WO2014076321A1 (en) * 2012-11-19 2014-05-22 Pieris Ag Novel specific-binding polypeptides and uses thereof

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE76311T1 (de) 1986-08-19 1992-06-15 Genentech Inc Einrichtung und dispersion zum intrapulmonalen eingeben von polypeptidwuchsstoffen und zytokinen.
JPH01215289A (ja) 1988-02-22 1989-08-29 Toa Nenryo Kogyo Kk 遺伝子組換えによる正常ヒト血清アルブミンaの製造方法
FR2649991B2 (fr) 1988-08-05 1994-03-04 Rhone Poulenc Sante Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces
US5728553A (en) 1992-09-23 1998-03-17 Delta Biotechnology Limited High purity albumin and method of producing
MX9605717A (es) 1994-05-18 1998-05-31 Inhale Therapeutic Syst Metodos y composiciones para la formulacion de polvo seco de interferones.
DE4417598A1 (de) 1994-05-19 1995-12-14 Max Planck Gesellschaft Verwendung des Tetracyclinpromotors zur stringent regulierten Produktion von rekombinanten Proteinen in prokaryontischen Zellen
AU5132096A (en) 1995-01-30 1996-08-21 Terrapin Technologies, Inc. Glubodies - multiplicities of proteins capable of binding a variety of small molecules
US5908621A (en) 1995-11-02 1999-06-01 Schering Corporation Polyethylene glycol modified interferon therapy
US6620413B1 (en) 1995-12-27 2003-09-16 Genentech, Inc. OB protein-polymer chimeras
DE19641876B4 (de) 1996-10-10 2011-09-29 Iba Gmbh Streptavidinmuteine
WO1998016873A1 (en) 1996-10-14 1998-04-23 Firm Forsat Ltd. Method for preparing dispersions of chromogenic components
DE19742706B4 (de) 1997-09-26 2013-07-25 Pieris Proteolab Ag Lipocalinmuteine
GB9722131D0 (en) 1997-10-20 1997-12-17 Medical Res Council Method
CA2233725A1 (en) 1998-03-31 1999-09-30 Hemosol Inc. Hemoglobin-hydroxyethyl starch complexes
DK1087778T3 (da) 1998-06-08 2005-12-19 Hoffmann La Roche Anvendelse af PEG-IFN-alfa og Ribavirin til behandling af kronisk hepatitis C
US6403564B1 (en) 1998-10-16 2002-06-11 Schering Corporation Ribavirin-interferon alfa combination therapy for eradicating detectable HCV-RNA in patients having chronic hepatitis C infection
DE19926068C1 (de) 1999-06-08 2001-01-11 Arne Skerra Muteine des Bilin-Bindungsproteins
AU2001294617A1 (en) 2000-09-21 2002-04-02 University Of Massachusetts Method of inducing apoptosis in lymphoid cells
AU2002335930B2 (en) 2001-03-09 2005-07-28 Morphosys Ag Serum albumin binding moieties
WO2003029462A1 (en) 2001-09-27 2003-04-10 Pieris Proteolab Ag Muteins of human neutrophil gelatinase-associated lipocalin and related proteins
WO2003029471A1 (en) 2001-09-27 2003-04-10 Pieris Proteolab Ag Muteins of apolipoprotein d
WO2005019255A1 (en) 2003-08-25 2005-03-03 Pieris Proteolab Ag Muteins of tear lipocalin
AU2003264100A1 (en) 2003-08-25 2005-03-10 Pieris Proteolab Ag Muteins of a bilin-binding protein with affinity for a given target
JP2007284351A (ja) 2004-07-27 2007-11-01 Osaka Bioscience Institute アミロイド蛋白質の凝集を抑制する物質とその作用
US7892827B2 (en) 2004-11-26 2011-02-22 Pieris Ag Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4)
JP2009509535A (ja) 2005-09-27 2009-03-12 アムニクス, インコーポレイテッド タンパク様薬剤およびその使用
US20070087005A1 (en) 2005-10-14 2007-04-19 Lazar Gregory A Anti-glypican-3 antibody
WO2007137170A2 (en) 2006-05-20 2007-11-29 Seattle Genetics, Inc. Anti-glypican-3 antibody drug conjugates
EP2046820B1 (en) 2006-08-01 2010-10-20 Pieris AG Muteins of tear lipocalin and methods for obtaining the same
ME02345B (me) 2007-07-17 2016-08-31 Squibb & Sons Llc MONOKLONSKA ANTlTELA PROTIV GLIPIKANA-3
WO2009052400A1 (en) 2007-10-19 2009-04-23 Abbott Laboratories Antibodies that bind to mammalian ngal and uses thereof
DK3381933T3 (da) 2008-06-24 2020-08-03 Technische Universität München Muteiner af hngal og relaterede proteiner med affinitet til et givet mål
RU2707126C2 (ru) 2009-12-07 2019-11-22 Пирис Аг МУТЕИНЫ ЛИПОКАЛИНА 2 ЧЕЛОВЕКА (Lcn2, hNGAL) С АФФИННОСТЬЮ ДЛЯ ОПРЕДЕЛЕННОЙ МИШЕНИ
WO2011149962A1 (en) 2010-05-24 2011-12-01 The Trustees Of Columbia University In The City Of New York Mutant ngal proteins and uses thereof
PL2580236T3 (pl) 2010-06-08 2019-09-30 Pieris Pharmaceuticals Gmbh Muteiny lipokaliny łez wiążące IL-4 R alfa
EP3299386A1 (en) 2010-08-16 2018-03-28 Pieris Pharmaceuticals GmbH Binding proteins for hepcidin
US20130225505A1 (en) 2011-11-23 2013-08-29 Allergan, Inc. Muteins of human tear lipcalin for treating neovascular disease of the anterior segment of the human eye
JP6839087B2 (ja) 2015-01-28 2021-03-03 ピエリス ファーマシューティカルズ ゲーエムベーハー 血管新生に特異的な新規のタンパク質
CR20170425A (es) 2015-02-18 2017-11-22 Sanofi Sa Nuevas proteínas específicas para pioverdina y pioquelina
CN114573680A (zh) 2015-05-04 2022-06-03 皮里斯制药有限公司 Cd137特异性的蛋白
MX2017014730A (es) 2015-05-18 2018-06-28 Pieris Pharmaceuticals Gmbh Muteinas de lipocalina 2 humana con afinidad por glipicano-3 (gpc3).

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2395519C2 (ru) * 2005-08-09 2010-07-27 Онкотерапи Сайенс, Инк. Глипикан-3 (gpc3)-производные антигенные пептиды, отторгающие опухоли, используемые для нla-a2-положительных пациентов, и фармацевтическая продукция, включающая их
WO2007107563A2 (en) * 2006-03-20 2007-09-27 Technische Universität München Muteins of tear lipocalin with affinity for the t-cell coreceptor cd4
WO2012065978A1 (en) * 2010-11-15 2012-05-24 Pieris Ag Muteins of human lipocalin 2 with affinity for glypican-3 (gpc3)
WO2013174783A1 (en) * 2012-05-23 2013-11-28 Pieris Ag Lipocalin muteins with binding-affinity for glypican-3 (gpc-3) and use of lipocalin muteins for target-specific delivery to cells expressing gpc-3
WO2014076321A1 (en) * 2012-11-19 2014-05-22 Pieris Ag Novel specific-binding polypeptides and uses thereof

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
ARNAU J. et al., Current strategies for the use of affinity tags and tag removal for the purification of recombinant proteins, Protein expression and purification, 2006, V. 48, N. 1, p.1-13. *
FRANKEL A.E. et al., Characterization of diphtheria fusion proteins targeted to the human interleukin-3 receptor, Protein Eng., 2000, v.13, n.8, p.575-581; *
FRANKEL A.E. et al., Characterization of diphtheria fusion proteins targeted to the human interleukin-3 receptor, Protein Eng., 2000, v.13, n.8, p.575-581; ORLANDO M., Modification of proteins and low molecular weight substances with hydroxyethyl starch (HES), Inauguraldissertation, Giesen, 2003, p.166; ARNAU J. et al., Current strategies for the use of affinity tags and tag removal for the purification of recombinant proteins, Protein expression and purification, 2006, V. 48, N. 1, p.1-13. *
ORLANDO M., Modification of proteins and low molecular weight substances with hydroxyethyl starch (HES), Inauguraldissertation, Giesen, 2003, p.166; *
WU Н. et al., Humanization of a Murine Monoclonal Antibody by Simultaneous Optimization of Framework and CDR Residues, J. Mol. Biol, 1999, Vol. 294, pp. 151-162 *
WU Н. et al., Humanization of a Murine Monoclonal Antibody by Simultaneous Optimization of Framework and CDR Residues, J. Mol. Biol, 1999, Vol. 294, pp. 151-162; *

Also Published As

Publication number Publication date
US20180141988A1 (en) 2018-05-24
CN107787327B (zh) 2022-02-08
AU2016262838B2 (en) 2020-10-08
JP2021184725A (ja) 2021-12-09
SG11201707872WA (en) 2017-10-30
JP6942060B2 (ja) 2021-09-29
KR20180008649A (ko) 2018-01-24
CA2982034A1 (en) 2016-11-24
AU2016262838A1 (en) 2018-01-04
BR112017020961A2 (pt) 2018-07-10
CN114456252A (zh) 2022-05-10
ZA201706605B (en) 2020-05-27
JP2018519802A (ja) 2018-07-26
US10273275B2 (en) 2019-04-30
CN107787327A (zh) 2018-03-09
WO2016184875A1 (en) 2016-11-24
EP3298029A1 (en) 2018-03-28
US20190309037A1 (en) 2019-10-10
MX2017014730A (es) 2018-06-28
RU2017135605A3 (enExample) 2019-11-13
US10787491B2 (en) 2020-09-29
JP7217783B2 (ja) 2023-02-03
RU2017135605A (ru) 2019-06-18

Similar Documents

Publication Publication Date Title
RU2756318C2 (ru) Мутеины липокалина 2 человека с аффинностью в отношении глипикана-3 (gpc3)
JP6766194B2 (ja) IL−4Rαに結合する涙液リポカリンムテイン
EP2640740B1 (en) Muteins of human lipocalin 2 with affinity for glypican-3 (gpc3)
RU2515063C2 (ru) Мутеины липокалина слезной жидкости, обладающие аффинностью к с-мет рецепторной тирозинкиназе человека и способы их получения
JP6843754B2 (ja) ピオベルジン及びピオケリンに特異的な新規なタンパク質
EP2990798B1 (en) Muteins of human lipocalin 2 (lcn2, hngal) with affinity for a given target