AU2014228962B2 - Multimerization technologies - Google Patents

Multimerization technologies Download PDF

Info

Publication number
AU2014228962B2
AU2014228962B2 AU2014228962A AU2014228962A AU2014228962B2 AU 2014228962 B2 AU2014228962 B2 AU 2014228962B2 AU 2014228962 A AU2014228962 A AU 2014228962A AU 2014228962 A AU2014228962 A AU 2014228962A AU 2014228962 B2 AU2014228962 B2 AU 2014228962B2
Authority
AU
Australia
Prior art keywords
antibody
component
cells
binding agent
seq
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
AU2014228962A
Other languages
English (en)
Other versions
AU2014228962A1 (en
Inventor
Mahiuddin Ahmed
Nai-Kong V. Cheung
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.)
Memorial Sloan Kettering Cancer Center
Original Assignee
Memorial Sloan Kettering Cancer Center
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 Memorial Sloan Kettering Cancer Center filed Critical Memorial Sloan Kettering Cancer Center
Publication of AU2014228962A1 publication Critical patent/AU2014228962A1/en
Application granted granted Critical
Publication of AU2014228962B2 publication Critical patent/AU2014228962B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2809—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3053—Skin, nerves, brain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3076—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties
    • C07K16/3084—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties against tumour-associated gangliosides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • 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
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • 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
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • 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
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor

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)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Toxicology (AREA)
  • Endocrinology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
AU2014228962A 2013-03-15 2014-03-14 Multimerization technologies Active AU2014228962B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361791600P 2013-03-15 2013-03-15
US61/791,600 2013-03-15
PCT/US2014/029041 WO2014144573A2 (en) 2013-03-15 2014-03-14 Multimerization technologies

Publications (2)

Publication Number Publication Date
AU2014228962A1 AU2014228962A1 (en) 2015-09-10
AU2014228962B2 true AU2014228962B2 (en) 2019-03-14

Family

ID=51538343

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2014228962A Active AU2014228962B2 (en) 2013-03-15 2014-03-14 Multimerization technologies

Country Status (10)

Country Link
US (2) US9802995B2 (enExample)
EP (1) EP2968547B1 (enExample)
JP (1) JP6480907B2 (enExample)
KR (1) KR102090356B1 (enExample)
CN (1) CN105530959B (enExample)
AU (1) AU2014228962B2 (enExample)
BR (1) BR112015022978A8 (enExample)
CA (1) CA2902561C (enExample)
RU (1) RU2714733C2 (enExample)
WO (1) WO2014144573A2 (enExample)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2014228772B2 (en) * 2013-03-15 2019-02-28 Memorial Sloan Kettering Cancer Center High affinity anti-GD2 antibodies
CN105530959B (zh) 2013-03-15 2021-09-17 纪念斯隆-凯特琳癌症中心 多聚化技术
HRP20201914T1 (hr) 2013-05-06 2021-01-22 Scholar Rock, Inc. Sastavi i postupci za modulaciju faktora rasta
US10370776B2 (en) * 2013-09-25 2019-08-06 Idea Orchard, Llc Antibody like protein
MX2017006167A (es) 2014-11-12 2018-03-23 Siamab Therapeutics Inc Compuestos que interactúan con glicanos y métodos de uso.
WO2017055385A1 (en) * 2015-10-02 2017-04-06 F. Hoffmann-La Roche Ag Anti-cd3xgd2 bispecific t cell activating antigen binding molecules
CA3002097A1 (en) 2015-11-12 2017-05-18 Siamab Therapeutics, Inc. Glycan-interacting compounds and methods of use
EP3526257A2 (en) * 2016-10-14 2019-08-21 Dana-Farber Cancer Institute, Inc. Modular tetravalent bispecific antibody platform
WO2018094143A1 (en) * 2016-11-17 2018-05-24 Siamab Therapeutics, Inc. Glycan-interacting compounds and methods of use
CN108264568B (zh) * 2016-12-30 2021-11-16 博晟生医股份有限公司 重组多肽、核酸分子及其组合物以及制造、使用其的方法
US11046768B2 (en) 2017-01-27 2021-06-29 Memorial Sloan Kettering Cancer Center Bispecific HER2 and CD3 binding molecules
WO2018152530A1 (en) * 2017-02-20 2018-08-23 Adimab, Llc Proteins binding gd2, nkg2d and cd16
KR20240044544A (ko) 2017-03-03 2024-04-04 씨젠 인크. 글리칸-상호작용 화합물 및 사용 방법
CN108690138A (zh) * 2017-04-12 2018-10-23 鸿运华宁（杭州）生物医药有限公司 一种能与人cd19或cd20和人cd3结合的双特异性抗体及其应用
WO2019133847A1 (en) * 2017-12-29 2019-07-04 Oncorus, Inc. Oncolytic viral delivery of therapeutic polypeptides
JPWO2020071554A1 (ja) * 2018-10-05 2021-09-09 北海道公立大学法人 札幌医科大学 がん幹細胞特異的抗体
JP2022510218A (ja) * 2018-11-30 2022-01-26 メモリアル スローン ケタリング キャンサー センター ヘテロ二量体四価特異性抗体およびこれらの使用
WO2020172259A1 (en) * 2019-02-20 2020-08-27 Research Institute At Nationwide Children's Hospital Cancer-targeted, virus-encoded, regulatable t (catvert) or nk cell (catvern) linkers
EP3966227A1 (en) 2019-05-07 2022-03-16 Voyager Therapeutics, Inc. Compositions and methods for the vectored augmentation of protein destruction, expression and/or regulation
JP7137696B2 (ja) 2019-05-14 2022-09-14 プロヴェンション・バイオ・インコーポレイテッド １型糖尿病を予防するための方法および組成物
KR20230092863A (ko) 2020-06-11 2023-06-26 프로벤션 바이오, 인코포레이티드 제1형 당뇨병을 예방하기 위한 방법 및 조성물
EP4175656A4 (en) * 2020-07-03 2024-10-16 The Trustees of Columbia University in the City of New York POLYFUNCTIONAL ORTHOGONAL PROTEIN CHIMERA
MX2023013851A (es) 2021-05-24 2023-12-08 Provention Bio Inc Metodos para el tratamiento de diabetes tipo 1.
WO2023023055A1 (en) 2021-08-16 2023-02-23 Renagade Therapeutics Management Inc. Compositions and methods for optimizing tropism of delivery systems for rna
TW202328067A (zh) 2021-09-14 2023-07-16 美商雷納嘉德醫療管理公司 環狀脂質及其使用方法
WO2023044343A1 (en) 2021-09-14 2023-03-23 Renagade Therapeutics Management Inc. Acyclic lipids and methods of use thereof
WO2023122752A1 (en) 2021-12-23 2023-06-29 Renagade Therapeutics Management Inc. Constrained lipids and methods of use thereof
CA3255619A1 (en) 2022-04-07 2023-10-12 Renagade Therapeutics Management Inc. CYCLIC LIPIDS AND LIPID NANOPARTICLES (LPNs) FOR THE SUPPLY OF NUCLEIC ACIDS OR PEPTIDES INTENDED FOR USE IN VACCINATION AGAINST INFECTIOUS AGENTS
US20260021206A1 (en) * 2022-07-25 2026-01-22 Vironexis Biotherapeutics Inc. Adeno-associated virus vectors and methods of their use for reducing the risk of, treating, and preventing metastasis
CU20230043A7 (es) * 2023-09-08 2025-04-04 Ct Inmunologia Molecular Anticuerpos biespecíficos que unen cd3 y el gangliósido ngcgm3

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060228300A1 (en) * 2005-04-06 2006-10-12 Ibc Pharmaceuticals, Inc. Stably tethered structures of defined compositions with multiple functions or binding specificities

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2326389C (en) * 1998-04-21 2007-01-23 Micromet Gesellschaft Fur Biomedizinische Forschung Mbh Novel cd19xcd3 specific polypeptides and uses thereof
GB0015119D0 (en) * 2000-06-20 2000-08-09 Angeletti P Ist Richerche Bio Methods and means for regulation of gene expression
GB0230202D0 (en) * 2002-12-27 2003-02-05 Domantis Ltd Ligand
ATE346866T1 (de) 2001-09-14 2006-12-15 Affimed Therapeutics Ag Multimerische, einzelkettige, tandem-fv- antikörper
US20070298041A1 (en) * 2002-06-28 2007-12-27 Tomlinson Ian M Ligands That Enhance Endogenous Compounds
CN1678634A (zh) * 2002-06-28 2005-10-05 多曼蒂斯有限公司 免疫球蛋白单个变体抗原结合区及其特异性构建体
EP1771205B1 (en) * 2004-06-18 2016-10-26 Ambrx, Inc. Novel antigen-binding polypeptides and their uses
AU2006232310B9 (en) * 2005-04-06 2011-07-21 Ibc Pharmaceuticals, Inc. Improved stably tethered structures of defined compositions with multiple functions or binding specificities
EP2050764A1 (en) * 2007-10-15 2009-04-22 sanofi-aventis Novel polyvalent bispecific antibody format and uses thereof
NZ603581A (en) * 2010-06-19 2015-05-29 Sloan Kettering Inst Cancer Anti-gd2 antibodies
CN105530959B (zh) 2013-03-15 2021-09-17 纪念斯隆-凯特琳癌症中心 多聚化技术

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060228300A1 (en) * 2005-04-06 2006-10-12 Ibc Pharmaceuticals, Inc. Stably tethered structures of defined compositions with multiple functions or binding specificities

Also Published As

Publication number Publication date
CA2902561A1 (en) 2014-09-18
KR20150132420A (ko) 2015-11-25
HK1216145A1 (en) 2016-10-21
EP2968547A4 (en) 2016-11-09
RU2714733C2 (ru) 2020-02-19
JP6480907B2 (ja) 2019-03-13
EP2968547A2 (en) 2016-01-20
WO2014144573A2 (en) 2014-09-18
BR112015022978A2 (pt) 2017-11-14
KR102090356B1 (ko) 2020-03-18
AU2014228962A1 (en) 2015-09-10
WO2014144573A3 (en) 2015-10-29
CN105530959B (zh) 2021-09-17
US20160168211A1 (en) 2016-06-16
US20180251503A1 (en) 2018-09-06
US9802995B2 (en) 2017-10-31
CN105530959A (zh) 2016-04-27
RU2015143166A (ru) 2017-04-20
JP2016516049A (ja) 2016-06-02
EP2968547B1 (en) 2019-08-07
BR112015022978A8 (pt) 2018-01-23
CA2902561C (en) 2022-08-02

Similar Documents

Publication Publication Date Title
US9802995B2 (en) Antibody multimerization technologies
JP7465833B2 (ja) Ｃｄ３反応性に基づくｔ細胞リクルートポリペプチド
KR102629403B1 (ko) Vista 항원 결합 분자
EP4245317A1 (en) Bispecific antibody for claudin 18a2 and cd3 and application of bispecific antibody
US12258405B2 (en) CD3 antibody and pharmaceutical use thereof
AU2018274919A1 (en) Bispecific heterodimeric diabodies and uses thereof
TW202033218A (zh) 多特異性蛋白分子
KR20210121141A (ko) Cd3-특이적 결합 분자
JP7851303B2 (ja) ヒトｃｄ３イプシロンに結合する新規なヒト抗体
WO2016077638A1 (en) Anti-chondroitin sulfate proteoglycan 4 antibodies and uses thereof
TW202304997A (zh) 新型抗ｃｄ４抗體
WO2023143535A1 (zh) 一种靶向il-18bp的抗体及其应用
US20250101104A1 (en) Bispecific molecule with tunable affinity to a targeted antigen
US10626183B2 (en) IFN-γ-inducible regulatory T cell convertible anti-cancer (IRTCA) antibody and uses thereof
HK1216145B (en) Multimerization technologies
HK40120054A (en) T cell recruiting polypeptides based on cd3 reactivity
WO2025238157A1 (en) Multispecific binding agent suitable for use in cancer immune therapy
CN121159699A (zh) 抗Trop2/CD3的双特异性抗体及其应用

Legal Events

Date Code Title Description
FGA Letters patent sealed or granted (standard patent)