CN113544156A - 抗Claudin18.2抗体及其应用 - Google Patents

抗Claudin18.2抗体及其应用 Download PDF

Info

Publication number
CN113544156A
CN113544156A CN202080019073.9A CN202080019073A CN113544156A CN 113544156 A CN113544156 A CN 113544156A CN 202080019073 A CN202080019073 A CN 202080019073A CN 113544156 A CN113544156 A CN 113544156A
Authority
CN
China
Prior art keywords
variable region
chain variable
seq
antibody
heavy chain
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.)
Granted
Application number
CN202080019073.9A
Other languages
English (en)
Other versions
CN113544156B (zh
Inventor
杨阳
葛虎
陶维康
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.)
Jiangsu Hengrui Medicine Co Ltd
Shanghai Hengrui Pharmaceutical Co Ltd
Original Assignee
Jiangsu Hengrui Medicine Co Ltd
Shanghai Hengrui Pharmaceutical Co Ltd
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 Jiangsu Hengrui Medicine Co Ltd, Shanghai Hengrui Pharmaceutical Co Ltd filed Critical Jiangsu Hengrui Medicine Co Ltd
Priority to CN202211305192.8A priority Critical patent/CN116063516A/zh
Publication of CN113544156A publication Critical patent/CN113544156A/zh
Application granted granted Critical
Publication of CN113544156B publication Critical patent/CN113544156B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/68—Medicinal 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • 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
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], 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 [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
    • C07K16/467—Igs with modifications in the FR-residues only
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • 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
    • C07K2317/20—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
    • C07K2317/50—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
    • 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
    • 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
    • C07K2317/50—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
    • C07K2317/567—Framework region [FR]
    • 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
    • C07K2317/70—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
    • C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
    • 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
    • C07K2317/77—Internalization into the cell
    • 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)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pathology (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本公开涉及抗Claudin18.2抗体及其应用。具体地，本发明涉及一种抗Claudin18.2抗体；包含所述抗Claudin18.2抗体CDR的鼠源抗体、嵌合抗体、人源化抗体及其抗原结合片段，以及其作为药物的用途。特别地，本公开涉及一种抗Claudin18.2抗体在制备用于治疗Claudin18.2阳性疾病或病症的药物中的用途。

Description

PCT国内申请，说明书已公开。

Claims (17)

  1. PCT国内申请，权利要求书已公开。
CN202080019073.9A 2019-04-01 2020-03-31 抗Claudin18.2抗体及其应用 Active CN113544156B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202211305192.8A CN116063516A (zh) 2019-04-01 2020-03-31 抗Claudin18.2抗体及其应用

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN201910257853 2019-04-01
CN2019102578536 2019-04-01
PCT/CN2020/082369 WO2020200196A1 (zh) 2019-04-01 2020-03-31 抗Claudin18.2抗体及其应用

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN202211305192.8A Division CN116063516A (zh) 2019-04-01 2020-03-31 抗Claudin18.2抗体及其应用

Publications (2)

Publication Number Publication Date
CN113544156A true CN113544156A (zh) 2021-10-22
CN113544156B CN113544156B (zh) 2022-11-22

Family

ID=72664673

Family Applications (2)

Application Number Title Priority Date Filing Date
CN202211305192.8A Pending CN116063516A (zh) 2019-04-01 2020-03-31 抗Claudin18.2抗体及其应用
CN202080019073.9A Active CN113544156B (zh) 2019-04-01 2020-03-31 抗Claudin18.2抗体及其应用

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CN202211305192.8A Pending CN116063516A (zh) 2019-04-01 2020-03-31 抗Claudin18.2抗体及其应用

Country Status (12)

Country Link
US (1) US20220185881A1 (zh)
EP (1) EP3950716A4 (zh)
JP (1) JP2022528061A (zh)
KR (1) KR20210148216A (zh)
CN (2) CN116063516A (zh)
AU (1) AU2020250601A1 (zh)
BR (1) BR112021019135A2 (zh)
CA (1) CA3134411A1 (zh)
MX (1) MX2021011489A (zh)
TW (1) TW202102546A (zh)
WO (1) WO2020200196A1 (zh)
ZA (1) ZA202106880B (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115947855A (zh) * 2022-05-20 2023-04-11 杭州邦顺制药有限公司 抗cd24抗体的制备及其用途

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG11202108398YA (en) 2019-02-01 2021-08-30 Novarock Biotherapeutics Ltd Anti-claudin 18 antibodies and methods of use thereof
CA3156803A1 (en) 2019-10-03 2021-04-08 Atyr Pharma, Inc. Compositions and methods comprising anti-nrp2 antibodies
EP4074345A4 (en) * 2019-12-12 2023-10-25 Jiangsu Hengrui Pharmaceuticals Co., Ltd. ANTI-CLAUDINE ANTIBODY-DRUG CONJUGATE AND ITS PHARMACEUTICAL USE
KR20230113578A (ko) * 2020-11-27 2023-07-31 선샤인 레이크 파르마 컴퍼니 리미티드 Cldn18.2 항체 및 그의 용도
WO2022122709A1 (en) 2020-12-07 2022-06-16 Sotio Biotech A.S. Antibody-drug conjugates based on humanized cldn18.2 antibodies
CN114634566B (zh) * 2020-12-16 2023-09-19 广州百暨基因科技有限公司 一种抗Claudin18_2的抗原结合片段、抗体及其应用
EP4267194A1 (en) 2020-12-23 2023-11-01 SOTIO Biotech a.s. Tumor-specific claudin 18.2 antibody-drug conjugates
CN114685682B (zh) * 2020-12-31 2023-11-10 上海莱馥医疗科技有限公司 一种靶向表达cldn 18.2的细胞的嵌合抗原受体
EP4304658A1 (en) * 2021-03-08 2024-01-17 Genequantum Healthcare (Suzhou) Co., Ltd. Antibody-immune agonist conjugate and applications thereof
CN113416260B (zh) * 2021-04-14 2022-02-01 南京凯地医疗技术有限公司 靶向Claudin18.2的特异性嵌合抗原受体细胞及其制备方法和应用
WO2023076998A1 (en) * 2021-10-27 2023-05-04 Atyr Pharma, Inc. COMPOSITIONS AND METHODS COMPRISING ANTI-NRP2a ANTIBODIES

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104321345A (zh) * 2012-05-09 2015-01-28 加尼梅德药物公司 用于癌症诊断的针对密蛋白18.2的抗体
CN104379166A (zh) * 2012-05-23 2015-02-25 加尼梅德药物公司 用于治疗癌症的涉及针对密蛋白18.2之抗体的联合治疗
WO2018006882A1 (zh) * 2016-07-08 2018-01-11 科济生物医药（上海）有限公司 抗密蛋白18a2的抗体及其应用
WO2018054484A1 (en) * 2016-09-23 2018-03-29 Biontech Ag Bispecific trivalent antibodies binding to claudin 6 or claudin18.2 and cd3 for treatment of claudin expressing cancer diseases

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
UA94628C2 (ru) 2006-10-27 2011-05-25 Дженентек, Инк. Гуманизированное моноклональное антитело, которое связывается с steap-1, и его применение
EP1997832A1 (en) * 2007-05-29 2008-12-03 Ganymed Pharmaceuticals AG Monoclonal antibodies against Claudin-18 for treatment of cancer
RU2708461C2 (ru) 2015-02-15 2019-12-09 Цзянсу Хэнжуй Медсин Ко., Лтд. Конъюгат лиганда с цитотоксическим лекарственным средством, способ его получения и применение
WO2016165762A1 (en) * 2015-04-15 2016-10-20 Ganymed Pharmaceuticals Ag Drug conjugates comprising antibodies against claudin 18.2
EP4074345A4 (en) * 2019-12-12 2023-10-25 Jiangsu Hengrui Pharmaceuticals Co., Ltd. ANTI-CLAUDINE ANTIBODY-DRUG CONJUGATE AND ITS PHARMACEUTICAL USE

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104321345A (zh) * 2012-05-09 2015-01-28 加尼梅德药物公司 用于癌症诊断的针对密蛋白18.2的抗体
CN104379166A (zh) * 2012-05-23 2015-02-25 加尼梅德药物公司 用于治疗癌症的涉及针对密蛋白18.2之抗体的联合治疗
WO2018006882A1 (zh) * 2016-07-08 2018-01-11 科济生物医药（上海）有限公司 抗密蛋白18a2的抗体及其应用
WO2018054484A1 (en) * 2016-09-23 2018-03-29 Biontech Ag Bispecific trivalent antibodies binding to claudin 6 or claudin18.2 and cd3 for treatment of claudin expressing cancer diseases

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BRYCE NELSON等: "Structure-Guided Combinatorial Engineering Facilitates Affinity and Specificity Optimization of Anti-CD81 Antibodies", 《JOURNAL OF MOLECULAR BIOLOGY》 *
徐良额等: "CLDN18.2 蛋白在恶性肿瘤治疗中的研究进展", 《中国肿瘤临床》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115947855A (zh) * 2022-05-20 2023-04-11 杭州邦顺制药有限公司 抗cd24抗体的制备及其用途
CN115947855B (zh) * 2022-05-20 2023-10-27 杭州邦顺制药有限公司 抗cd24抗体的制备及其用途

Also Published As

Publication number Publication date
WO2020200196A1 (zh) 2020-10-08
US20220185881A1 (en) 2022-06-16
TW202102546A (zh) 2021-01-16
BR112021019135A2 (pt) 2021-11-30
JP2022528061A (ja) 2022-06-08
MX2021011489A (es) 2021-10-22
ZA202106880B (en) 2023-02-22
KR20210148216A (ko) 2021-12-07
CA3134411A1 (en) 2020-10-08
EP3950716A1 (en) 2022-02-09
EP3950716A4 (en) 2022-11-09
CN113544156B (zh) 2022-11-22
CN116063516A (zh) 2023-05-05
AU2020250601A1 (en) 2021-11-18

Similar Documents

Publication Publication Date Title
CN113544156B (zh) 抗Claudin18.2抗体及其应用
JP7317272B2 (ja) Ｔｉｇｉｔ抗体、その抗原結合断片及びその医療用途 本願は、２０１９年９月２９日に出願された出願番号ｃｎ２０１７１０９０８５６５．３に基づいたものであり、その優先権を主張する。その開示は、その全体が参照により本明細書に組み込まれる。
KR102662387B1 (ko) B7-h3 항체, 이의 항원-결합 단편 및 이의 의학적 용도
CN110914304B (zh) Cd96抗体、其抗原结合片段及医药用途
US11359021B2 (en) PD-L1 antibody, antigen-binding fragment thereof, and pharmaceutical use thereof
TW201909926A (zh) Ｂ７ｈ３抗體－藥物偶聯物及其醫藥用途
CN113906053B (zh) 抗cea抗体及其应用
TW202017945A (zh) 抗ｃｄ７３抗體、其抗原結合片段及應用
WO2021098822A1 (zh) 一种双特异性抗体
WO2021190441A1 (zh) Cd47/人源化cd47抗体或其抗原结合片段、免疫活性片段及应用
KR101259239B1 (ko) ＰｃｒＶ에 대한 항체
TWI685504B (zh) 抗gitr抗體、其抗原結合片段及其醫藥用途
CN110606892B (zh) 一种高亲和力高生物活性的lag-3抗体及其应用
CN113597432B (zh) 抗EpCAM抗体及其应用
WO2022078424A1 (zh) 抗trop-2抗体、其抗原结合片段或其突变体、及其医药用途

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 40060501

Country of ref document: HK

GR01 Patent grant
GR01 Patent grant