JP7525471B2 - S.アウレウス(S.aureus)クランピング因子A(ClfA)に対する抗体 - Google Patents

S.アウレウス(S.aureus)クランピング因子A(ClfA)に対する抗体 Download PDF

Info

Publication number
JP7525471B2
JP7525471B2 JP2021503901A JP2021503901A JP7525471B2 JP 7525471 B2 JP7525471 B2 JP 7525471B2 JP 2021503901 A JP2021503901 A JP 2021503901A JP 2021503901 A JP2021503901 A JP 2021503901A JP 7525471 B2 JP7525471 B2 JP 7525471B2
Authority
JP
Japan
Prior art keywords
antibody
antigen
binding fragment
seq
amino acid
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
JP2021503901A
Other languages
English (en)
Japanese (ja)
Other versions
JP2021530244A5 (enExample
JP2021530244A (ja
Inventor
トカジク,クリスティーン
セルマン,ブレット
ザ サード,マーティン ボーロック
コルティ,ダヴィデ
ミノラ,アンドレア
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Humabs Biomed SA
Original Assignee
Humabs Biomed SA
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 Humabs Biomed SA filed Critical Humabs Biomed SA
Publication of JP2021530244A publication Critical patent/JP2021530244A/ja
Publication of JP2021530244A5 publication Critical patent/JP2021530244A5/ja
Priority to JP2024053871A priority Critical patent/JP7892714B2/ja
Application granted granted Critical
Publication of JP7525471B2 publication Critical patent/JP7525471B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Gram-positive bacteria
    • C07K16/1271—Micrococcaceae (F); Staphylococcaceae (F), e.g. Staphylococcus (G)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • 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
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/524—CH2 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/526—CH3 domain
    • 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]
    • 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
    • C07K2317/72—Increased effector function due to an Fc-modification
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Communicable Diseases (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
JP2021503901A 2018-07-24 2019-07-24 S.アウレウス(S.aureus)クランピング因子A(ClfA)に対する抗体 Active JP7525471B2 (ja)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2024053871A JP7892714B2 (ja) 2018-07-24 2024-03-28 S.アウレウス(S.aureus)クランピング因子A(ClfA)に対する抗体

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862702762P 2018-07-24 2018-07-24
US62/702,762 2018-07-24
PCT/US2019/043254 WO2020023644A2 (en) 2018-07-24 2019-07-24 Antibody directed against s. aureus clumping factor a (clfa)

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2024053871A Division JP7892714B2 (ja) 2018-07-24 2024-03-28 S.アウレウス(S.aureus)クランピング因子A(ClfA)に対する抗体

Publications (3)

Publication Number Publication Date
JP2021530244A JP2021530244A (ja) 2021-11-11
JP2021530244A5 JP2021530244A5 (enExample) 2022-08-01
JP7525471B2 true JP7525471B2 (ja) 2024-07-30

Family

ID=67539640

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2021503901A Active JP7525471B2 (ja) 2018-07-24 2019-07-24 S.アウレウス(S.aureus)クランピング因子A(ClfA)に対する抗体
JP2024053871A Active JP7892714B2 (ja) 2018-07-24 2024-03-28 S.アウレウス(S.aureus)クランピング因子A(ClfA)に対する抗体

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2024053871A Active JP7892714B2 (ja) 2018-07-24 2024-03-28 S.アウレウス(S.aureus)クランピング因子A(ClfA)に対する抗体

Country Status (10)

Country Link
US (3) US11155606B2 (enExample)
EP (1) EP3840838A2 (enExample)
JP (2) JP7525471B2 (enExample)
KR (1) KR102955585B1 (enExample)
CN (2) CN112672788B (enExample)
AU (1) AU2019309366B2 (enExample)
BR (1) BR112021001214A2 (enExample)
MX (1) MX2021000889A (enExample)
TW (1) TWI902669B (enExample)
WO (1) WO2020023644A2 (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2024105229A (ja) * 2018-07-24 2024-08-06 メディミューン,エルエルシー S.アウレウス(S.aureus)クランピング因子A(ClfA)に対する抗体

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2917360B1 (en) 2012-11-06 2020-01-08 Medlmmune, LLC Antibodies to s. aureus surface determinants
DE102018115012A1 (de) 2018-06-21 2019-12-24 Carl Zeiss Microscopy Gmbh Teilchenstrahlsystem
WO2020076790A1 (en) 2018-10-09 2020-04-16 Medimmune, Llc Antibodies directed against staphylococcus aureus leukotoxins
MX2021004173A (es) 2018-10-09 2021-09-08 Medimmune Llc Combinaciones de anticuerpos dirigidos contra staphylococcus aureus.
TWI743626B (zh) 2019-01-24 2021-10-21 德商卡爾蔡司多重掃描電子顯微鏡有限公司 包含多束粒子顯微鏡的系統、對3d樣本逐層成像之方法及電腦程式產品
DE102019008249B3 (de) 2019-11-27 2020-11-19 Carl Zeiss Multisem Gmbh Teilchenstrahl-System mit einer Multistrahl-Ablenkeinrichtung und einem Strahlfänger, Verfahren zum Betreiben des Teilchenstrahl-Systems und zugehöriges Computerprogrammprodukt
IL324469A (en) * 2023-05-09 2026-01-01 Astrazeneca Ab Anti-Pseudomonal bispecific antibodies with modified fc regions and methods of using them
WO2025149667A1 (en) 2024-01-12 2025-07-17 Pheon Therapeutics Ltd Antibody drug conjugates and uses thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017522000A (ja) 2014-05-16 2017-08-10 メディミューン,エルエルシー 新生児Fc受容体結合が改変されて治療および診断特性が強化された分子

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US7658921B2 (en) 2000-12-12 2010-02-09 Medimmune, Llc Molecules with extended half-lives, compositions and uses thereof
WO2002072600A2 (en) * 2001-01-26 2002-09-19 Inhibitex, Inc. Monoclonal antibodies to the clfa protein and method of use in treating or preventing infections
AU2002368077B2 (en) 2001-07-12 2010-03-04 Jefferson Foote Super humanized antibodies
US20030226155A1 (en) 2001-08-30 2003-12-04 Biorexis Pharmaceutical Corporation Modified transferrin-antibody fusion proteins
ATE458006T1 (de) 2003-05-14 2010-03-15 Kenta Biotech Ag Humaner monoklonaler antikörper spezifisch für lipopolysacchariden (lps) des serotyps iats o6 von pseudomonas aeruginosa
CN1324049C (zh) 2003-08-04 2007-07-04 中国疾病预防控制中心病毒病预防控制所 人源抗sars冠状病毒基因工程抗体
US20050226878A1 (en) 2003-12-02 2005-10-13 3M Innovative Properties Company Therapeutic combinations and methods including IRM compounds
TW200813091A (en) 2006-04-10 2008-03-16 Amgen Fremont Inc Targeted binding agents directed to uPAR and uses thereof
JP2009539979A (ja) 2006-06-12 2009-11-19 ナビ バイオファーマシューティカルズ ブドウ球菌感染症を治療および予防するための、α毒素の使用
JP5675109B2 (ja) 2007-02-20 2015-02-25 アナプティスバイオ インコーポレイティッド ライブラリーの生成方法及びその使用
JP5718640B2 (ja) 2007-08-21 2015-05-13 アムジエン・インコーポレーテツド ヒトc−fms抗原結合性タンパク質
KR20100072228A (ko) 2007-08-31 2010-06-30 유니버시티 오브 시카고 스타필로코커스 폐 질환 및 상태에 대한 면역화와 관련된 방법 및 조성물
KR20110044991A (ko) 2008-07-02 2011-05-03 이머전트 프로덕트 디벨롭먼트 시애틀, 엘엘씨 TNF-α 길항제 다-표적 결합 단백질
EP2208787A1 (en) 2009-01-19 2010-07-21 Université de Liège A recombinant alpha-hemolysin polypeptide of Staphylococcus aureus, having a deletion in the stem domain and heterologous sequences inserted
CN102387814A (zh) 2009-01-29 2012-03-21 米迪缪尼有限公司 延长体内半衰期的人抗il-6抗体及其在治疗肿瘤、自身免疫性疾病和炎症性疾病中的应用
AU2010251156C1 (en) 2009-05-18 2015-02-05 Julius-Maximilians-Universitat Wurzburg Antibodies or fragments thereof directed against a Staphylococcus aureus epitope of IsaA or IsaB
LT3444268T (lt) 2010-05-05 2022-04-11 New York University Staphylococcus aureus leukocidinai, terapinės kompozicijos ir jų panaudojimo būdai
RS58190B2 (sr) 2011-02-08 2021-08-31 Medimmune Llc Antitela koja specifično vezuju staphylococcus aureus alfa toksin i postupci njihove primene
EP3777885A1 (en) 2011-06-19 2021-02-17 New York University Methods of treating and preventing staphylococcus aureus infections and associated conditions
US9962419B2 (en) 2012-03-19 2018-05-08 Tecnifar—Industria Tecnica Farmaceutica, S.A. Technophage, Investigação E Desenvolvimento Em Biotecnologia, SA Compositions comprising cocktails of antibacterial phages and uses thereof for the treatment of bacterial infections
ES2912267T3 (es) 2012-11-06 2022-05-25 Medimmune Llc Métodos de tratamiento de enfermedades asociadas a S. aureus
EP2917360B1 (en) 2012-11-06 2020-01-08 Medlmmune, LLC Antibodies to s. aureus surface determinants
CN105873946A (zh) 2013-10-17 2016-08-17 阿尔萨尼斯生物科学有限责任公司 交叉反应性金黄色葡萄球菌抗体序列
AU2014363987A1 (en) 2013-12-09 2016-06-30 Janssen Biotech, Inc. Compositions and methods for phagocyte delivery of anti-staphylococcal agents
BR112016014163A2 (pt) 2013-12-19 2018-01-09 Arsanis Biosciences Gmbh anticorpos direcionados contra a toxina lukgh (lukab) de staphylococcus aureus e as sequências de anticorpos, seu uso no tratamento ou no diagnóstico de infecção por s. aureus, as preparações farmacêuticas e para diagnóstico, os ácidos nucleicos que codificam os anticorpos, o paratopo isolado dos anticorpos e o epítopo conformacional isolado
TWI719938B (zh) 2014-06-19 2021-03-01 美商麥迪紐有限責任公司 多重細菌感染之治療
AU2016249837A1 (en) 2015-04-17 2017-09-28 Arsanis Biosciences Gmbh Anti-staphylococcus aureus antibody combination preparation
US20190077851A1 (en) 2015-10-30 2019-03-14 Bruno Francois Methods of using anti-alpha toxin antibody
MX2021000889A (es) 2018-07-24 2021-04-28 Medimmune Llc Anticuerpo dirigido contra el factor de agregación a (clfa) de s. aureus.
MX2021004173A (es) 2018-10-09 2021-09-08 Medimmune Llc Combinaciones de anticuerpos dirigidos contra staphylococcus aureus.
WO2020076790A1 (en) 2018-10-09 2020-04-16 Medimmune, Llc Antibodies directed against staphylococcus aureus leukotoxins

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017522000A (ja) 2014-05-16 2017-08-10 メディミューン,エルエルシー 新生児Fc受容体結合が改変されて治療および診断特性が強化された分子

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,2017年,Vol. 61,DOI: 10.1128/AAC.00629-17

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2024105229A (ja) * 2018-07-24 2024-08-06 メディミューン,エルエルシー S.アウレウス(S.aureus)クランピング因子A(ClfA)に対する抗体
JP7892714B2 (ja) 2018-07-24 2026-07-21 メディミューン,エルエルシー S.アウレウス(S.aureus)クランピング因子A(ClfA)に対する抗体

Also Published As

Publication number Publication date
US20240352098A1 (en) 2024-10-24
WO2020023644A3 (en) 2020-03-19
TWI902669B (zh) 2025-11-01
CN119176871A (zh) 2024-12-24
CN112672788B (zh) 2024-09-17
AU2019309366A1 (en) 2021-02-18
CN112672788A (zh) 2021-04-16
TW202019956A (zh) 2020-06-01
EP3840838A2 (en) 2021-06-30
AU2019309366B2 (en) 2025-06-05
US11970527B2 (en) 2024-04-30
MX2021000889A (es) 2021-04-28
US20220073595A1 (en) 2022-03-10
WO2020023644A2 (en) 2020-01-30
KR102955585B1 (ko) 2026-04-21
BR112021001214A2 (pt) 2021-04-27
JP7892714B2 (ja) 2026-07-21
JP2021530244A (ja) 2021-11-11
CA3107463A1 (en) 2020-01-30
US20200048330A1 (en) 2020-02-13
US11155606B2 (en) 2021-10-26
KR20210035846A (ko) 2021-04-01
JP2024105229A (ja) 2024-08-06

Similar Documents

Publication Publication Date Title
US11970527B2 (en) Antibody directed against S. aureus clumping factor A (ClfA)
JP6723293B2 (ja) 黄色ブドウ球菌(Staphylococcus aureus)α毒素に特異的に結合する抗体及び使用方法
US11168133B2 (en) Combinations of anti-Staphylococcus aureus antibodies
JP7459075B2 (ja) スタフィロコッカス・アウレウス(Staphylococcus aureus)ロイコトキシンに対して向けられた抗体
JP7160484B2 (ja) 抗o1抗体およびその使用
KR20170136637A (ko) 항-스타필로코커스 아우레우스 항체 배합 제제
US20190077851A1 (en) Methods of using anti-alpha toxin antibody
CN106132988A (zh) 抗金黄色葡萄球菌lukgh(lukab)毒素的抗体和抗体序列
US20160075768A1 (en) Adjuvant therapy for staphylococcal infection with enterotoxin specific mabs
JP2021500865A (ja) スタフィロコッカス(Staphsylococcus)標的抗原および補体成分に結合する二重特異性抗原結合分子ならびにその使用
RU2818805C2 (ru) АНТИТЕЛО, НАПРАВЛЕННОЕ ПРОТИВ ФАКТОРА СЛИПАНИЯ А (ClfA) S. aureus
CN108064241A (zh) 针对金黄色葡萄球菌的免疫球蛋白结合蛋白的抗体
KR20240139083A (ko) Btla에 대한 항체 및 이의 용도
HK40009426A (zh) 抗o1抗体及其用途

Legal Events

Date Code Title Description
RD01 Notification of change of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7426

Effective date: 20210506

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A821

Effective date: 20210506

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20220722

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20220722

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20230623

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20230704

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20230928

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20231013

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20231128

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20240328

A911 Transfer to examiner for re-examination before appeal (zenchi)

Free format text: JAPANESE INTERMEDIATE CODE: A911

Effective date: 20240418

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20240618

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20240718

R150 Certificate of patent or registration of utility model

Ref document number: 7525471

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150