SG11201400289SA - Glycosylated polypeptide and drug composition containing said polypeptide - Google Patents

Glycosylated polypeptide and drug composition containing said polypeptide

Info

Publication number
SG11201400289SA
SG11201400289SA SG11201400289SA SG11201400289SA SG11201400289SA SG 11201400289S A SG11201400289S A SG 11201400289SA SG 11201400289S A SG11201400289S A SG 11201400289SA SG 11201400289S A SG11201400289S A SG 11201400289SA SG 11201400289S A SG11201400289S A SG 11201400289SA
Authority
SG
Singapore
Prior art keywords
polypeptide
composition containing
drug composition
glycosylated
glycosylated polypeptide
Prior art date
Application number
SG11201400289SA
Other languages
English (en)
Inventor
Hirofumi Ochiai
Taiji Shimoda
Kazuhiro Fukae
Masatoshi Maeda
Kazuyuki Ishii
Kenta Yoshida
Katsunari Tezuka
Keisuke Tazuru
Original Assignee
Glytech Inc
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 Glytech Inc filed Critical Glytech Inc
Publication of SG11201400289SA publication Critical patent/SG11201400289SA/en

Links

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
    • C07K14/575Hormones
    • C07K14/655Somatostatins
    • C07K14/6555Somatostatins at least 1 amino acid in D-form
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • 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
    • C07K14/575Hormones
    • C07K14/655Somatostatins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/549Sugars, nucleosides, nucleotides or nucleic acids
    • 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
    • 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
    • A61P1/04Drugs 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
    • 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
    • A61P1/12Antidiarrhoeals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/06Antiglaucoma agents or miotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/12Ophthalmic agents for cataracts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/02Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Endocrinology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Genetics & Genomics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Emergency Medicine (AREA)
SG11201400289SA 2011-09-04 2012-09-03 Glycosylated polypeptide and drug composition containing said polypeptide SG11201400289SA (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2011192202 2011-09-04
PCT/JP2012/072380 WO2013032011A1 (ja) 2011-09-04 2012-09-03 糖鎖付加ポリペプチドおよび当該ポリペプチドを含む医薬組成物

Publications (1)

Publication Number Publication Date
SG11201400289SA true SG11201400289SA (en) 2014-05-29

Family

ID=47756483

Family Applications (2)

Application Number Title Priority Date Filing Date
SG11201400289SA SG11201400289SA (en) 2011-09-04 2012-09-03 Glycosylated polypeptide and drug composition containing said polypeptide
SG10201601324VA SG10201601324VA (en) 2011-09-04 2012-09-03 Glycosylated polypeptide and drug composition containing said polypeptide

Family Applications After (1)

Application Number Title Priority Date Filing Date
SG10201601324VA SG10201601324VA (en) 2011-09-04 2012-09-03 Glycosylated polypeptide and drug composition containing said polypeptide

Country Status (14)

Country Link
US (2) US9422357B2 (da)
EP (1) EP2752424B1 (da)
JP (1) JP6178238B2 (da)
KR (1) KR102031998B1 (da)
CN (2) CN103930441B (da)
AU (1) AU2012302636B2 (da)
BR (1) BR112014004784A2 (da)
CA (1) CA2847334C (da)
DK (1) DK2752424T3 (da)
IN (1) IN2014CN02399A (da)
RU (1) RU2624034C2 (da)
SG (2) SG11201400289SA (da)
TW (1) TWI662966B (da)
WO (1) WO2013032011A1 (da)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013032011A1 (ja) * 2011-09-04 2013-03-07 株式会社糖鎖工学研究所 糖鎖付加ポリペプチドおよび当該ポリペプチドを含む医薬組成物
EP2752425A4 (en) 2011-09-04 2015-04-22 Glytech Inc GLYCOSYLATED POLYPEPTIDE AND MEDICAMENT COMPOSITION WITH THIS POLYPEPTIDE
CN111855827B (zh) * 2019-04-24 2022-09-16 岛津企业管理(中国)有限公司 多糖蛋白结合疫苗中多糖蛋白结合位点结合率的测定方法

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4000259A (en) * 1975-06-16 1976-12-28 American Home Products Corporation Cyclic dodecapeptide analogs of somatostatin and intermediates
US4380953A (en) 1978-09-11 1983-04-26 Filper Corporation Transfer mechanism in a peach pitter
US4310518A (en) 1979-10-31 1982-01-12 Merck & Co., Inc. Cyclic hexapeptide somatostatin analogs
US4235886A (en) 1979-10-31 1980-11-25 Merck & Co., Inc. Cyclic hexapeptide somatostatin analogs
US4280953A (en) * 1979-11-08 1981-07-28 The Salk Institute For Biological Studies Glycosylated analogs of somatostatin
US4316891A (en) * 1980-06-14 1982-02-23 The Salk Institute For Biological Studies Extended N-terminal somatostatin
LU85269A1 (fr) 1984-03-26 1985-10-14 Techland S A Composes nouveaux de somatostatine,procede pour leur synthese,preparation a usage veterinaire contenant lesdits composes et procede pour le traitement d'animaux
US4801575A (en) * 1986-07-30 1989-01-31 The Regents Of The University Of California Chimeric peptides for neuropeptide delivery through the blood-brain barrier
HU906340D0 (en) 1986-10-13 1991-04-29 Sandoz Ag Synthesis in solid phase for producing peptonic alcohols
PH30995A (en) 1989-07-07 1997-12-23 Novartis Inc Sustained release formulations of water soluble peptides.
WO1997007205A1 (en) * 1995-08-11 1997-02-27 Novo Nordisk A/S Method for preparing polypeptide variants
US5750499A (en) * 1995-10-18 1998-05-12 The Salk Institute For Biological Studies Receptor-selective somatostatin analogs
FI965181A (fi) 1996-12-20 1998-06-21 Map Medical Technologies Oy Polyalkoholi-peptidijohdannaiset
JP3385947B2 (ja) 1998-01-05 2003-03-10 松下電器産業株式会社 バルクフィーダ
AU5805500A (en) * 1999-07-07 2001-01-30 Maxygen Aps A method for preparing modified polypeptides
US20030036181A1 (en) * 2000-06-30 2003-02-20 Okkels Jens Sigurd Peptide extended glycosylated polypeptides
EP1381396B1 (en) * 2001-04-23 2009-04-01 Mallinckrodt Inc. Tc and re labeled radioactive glycosylated octreotide derivatives
WO2003008431A1 (fr) 2001-06-19 2003-01-30 Otsuka Chemical Co.,Ltd. Methode de production d'un derive d'asparagine de chaines des sucres
US7943763B2 (en) 2002-07-05 2011-05-17 Otsuka Chemical Holdings Co., Ltd. Process for preparing glycopeptides having asparagine-linked oligosaccharides, and the glycopeptides
TWI330641B (en) 2002-12-24 2010-09-21 Yasuhiro Kajihara Sugar chain asparagine derivatives
CN100413889C (zh) * 2002-12-24 2008-08-27 大塚化学株式会社 糖链天冬酰胺衍生物、糖链天冬酰胺和糖链以及它们的制造方法
KR100661212B1 (ko) 2002-12-26 2007-04-16 오츠카 가가쿠 가부시키가이샤 3분지형 당사슬 아스파라긴 유도체, 상기 당사슬아스파라긴, 상기 당사슬 및 그들의 제조방법
CA2514337C (en) 2003-02-04 2010-07-13 Otsuka Chemical Co., Ltd. Process for producing sugar chain asparagine derivative
WO2004101619A1 (ja) * 2003-05-15 2004-11-25 Shionogi Co., Ltd. 機能的糖ペプチドの合理的設計および合成
KR100731875B1 (ko) 2003-07-28 2007-06-25 오츠카 가가쿠 가부시키가이샤 아미노화 복합형 당사슬 유도체 및 그의 제조방법
KR100604994B1 (ko) * 2004-01-30 2006-07-26 한국생명공학연구원 알파1,6-만노실트랜스퍼라제를 코딩하는 한세눌라폴리모르파 기원의 신규 유전자 및 상기 유전자가 결손된한세눌라 폴리모르파 변이주를 이용한 재조합 당단백질생산 방법
TWI466897B (zh) 2005-07-19 2015-01-01 Glytech Inc 癌細胞之檢測方法、糖鏈之構造解析方法,以及糖鏈衍生物
US20070025910A1 (en) * 2005-07-29 2007-02-01 Norenberg Jeffrey P Anticancer therapy
EP1941902A1 (en) * 2007-01-02 2008-07-09 Novartis AG Use of Somatostatin analogs in cluster headache
AU2008264750C1 (en) * 2007-06-19 2013-01-10 Glytech, Inc. GLP-1 peptide having sugar chain attached thereto
US20110172165A1 (en) 2008-02-19 2011-07-14 Peter Artymiuk Modified linkers
AU2009261441B2 (en) * 2008-06-17 2013-01-10 Glytech, Inc. Oligosaccharide chain added glp-1 peptide
WO2009156511A2 (en) * 2008-06-27 2009-12-30 Novo Nordisk A/S N-glycosylated human growth hormone with prolonged circulatory half-life
EP2752425A4 (en) 2011-09-04 2015-04-22 Glytech Inc GLYCOSYLATED POLYPEPTIDE AND MEDICAMENT COMPOSITION WITH THIS POLYPEPTIDE
WO2013032011A1 (ja) * 2011-09-04 2013-03-07 株式会社糖鎖工学研究所 糖鎖付加ポリペプチドおよび当該ポリペプチドを含む医薬組成物

Also Published As

Publication number Publication date
CA2847334C (en) 2020-09-01
TWI662966B (zh) 2019-06-21
JP6178238B2 (ja) 2017-08-09
EP2752424B1 (en) 2019-09-11
CA2847334A1 (en) 2013-03-07
CN103930441A (zh) 2014-07-16
KR20140059829A (ko) 2014-05-16
IN2014CN02399A (da) 2015-06-19
KR102031998B1 (ko) 2019-10-14
WO2013032011A1 (ja) 2013-03-07
EP2752424A1 (en) 2014-07-09
US9422357B2 (en) 2016-08-23
AU2012302636B2 (en) 2016-09-15
CN107522779A (zh) 2017-12-29
CN103930441B (zh) 2017-11-17
SG10201601324VA (en) 2016-03-30
CN107522779B (zh) 2021-10-26
BR112014004784A2 (pt) 2017-03-21
US9937264B2 (en) 2018-04-10
RU2624034C2 (ru) 2017-06-30
TW201315478A (zh) 2013-04-16
DK2752424T3 (da) 2019-11-18
AU2012302636A1 (en) 2014-03-20
EP2752424A4 (en) 2015-04-22
US20170157260A1 (en) 2017-06-08
RU2014112046A (ru) 2015-11-27
US20140336116A1 (en) 2014-11-13
JPWO2013032011A1 (ja) 2015-03-23

Similar Documents

Publication Publication Date Title
IL262667B (en) An isolated polynucleotide encoding a polypeptide and a pharmaceutical composition containing the isolated polynucleotide
SG10201601327RA (en) Glycosylated polypeptide and drug composition containing said polypeptide
HK1199889A1 (en) Relaxin fusion polypeptides and uses thereof
ZA201305504B (en) Compositions containing glycosylated antibodies and uses thereof
IL279676A (en) Recombinant proteins and therapeutic uses
EP2728002A4 (en) HETERODIMIZED POLYPEPTIDE
EP2718317A4 (en) GLUCOSE-DEPENDENT INSULINOTROPE POLYPEPTIDE ANALOGUE, PHARMACEUTICAL COMPOSITIONS AND THEIR USE
EP2738255A4 (en) PEPTIDE FROM ERAP1 AND ITS USE
SG11201405578TA (en) Pharmaceutical composition containing peptide
ZA201302113B (en) Caspofungin composition
EP2718283A4 (en) INDAZOLE AND PYRROLOPYRIDINE DERIVATIVE AND PHARMACEUTICAL USE THEREOF
EP2775831A4 (en) PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
ZA201207375B (en) Stabilized pharmaceutical composition
SG11201402139UA (en) High mast2-affinity polypeptides and uses thereof
EP2666482A4 (en) PARTICLE COMPOSITION AND PHARMACEUTICAL COMPOSITION WITH PARTICLE COMPOSITION
HK1198910A1 (en) Pharmaceutical composition comprising ebastine and fluticasone
SG11201400289SA (en) Glycosylated polypeptide and drug composition containing said polypeptide
SG11201401071YA (en) Glycosylated polypeptide and pharmaceutical composition containing same
IL221501A (en) Medicinal product containing miramistine
EP2743252A4 (en) TETRAVALENT PLATINUM COMPLEX AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
PL2918267T3 (pl) Kompozycja farmaceutyczna w postaci cząstek stałych
EP2751129A4 (en) PROTEIN P14 WITH CANCER, ANTIALLERGIC EFFECT AND PHARMACEUTICAL COMPOSITION THEREWITH
ZA201309537B (en) Pharmaceutical composition comprising fexofedine