CU23943B1 - Depsipéptidos cíclicos - Google Patents

Depsipéptidos cíclicos

Info

Publication number
CU23943B1
CU23943B1 CU2010000032A CU20100032A CU23943B1 CU 23943 B1 CU23943 B1 CU 23943B1 CU 2010000032 A CU2010000032 A CU 2010000032A CU 20100032 A CU20100032 A CU 20100032A CU 23943 B1 CU23943 B1 CU 23943B1
Authority
CU
Cuba
Prior art keywords
disease
diseases
depsypeptides
well
syndrome
Prior art date
Application number
CU2010000032A
Other languages
English (en)
Other versions
CU20100032A7 (es
Inventor
Philipp Krastel
Brigitta-Maria Liechty
Esther Schmitt
Erwin Paul Schreiner
Josef Gottfried Meingassner
Original Assignee
Novartis Ag
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=38805728&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CU23943(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Novartis Ag filed Critical Novartis Ag
Publication of CU20100032A7 publication Critical patent/CU20100032A7/es
Publication of CU23943B1 publication Critical patent/CU23943B1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/50—Cyclic peptides containing at least one abnormal peptide link
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/15—Depsipeptides; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K11/00—Depsipeptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K11/02—Depsipeptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof cyclic, e.g. valinomycins ; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Pulmonology (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Hydrogenated Pyridines (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

La presente solicitud se refiere a depsipéptidos cíclicos, que tienen la estructura de la fórmula (I), activos como inhibidores de calicreína 7 y elastasa de neutrófilos humanos. Los depsipéptidos de la invención son útiles en la fabricación de medicamentos para el tratamiento de enfermedades de la piel, inflamatorias y/o proliferativas y pruríticas tales como queloides, escaras, hipertróficas, acné, dermatitis atópica, psoriasis, psoriasis pustular, rosácea, síndrome de Netherton u otras dermatosis pruríticas tales como prurigo nodularis, comezón no especificada de los ancianos, así como otras enfermedades con mal funcionamiento de la barrera epitelial tal como piel envejecida, enfermedad inflamatoria del intestino y enfermedad de Crohn, así como pancreatitis, o de cáncer, en particular cáncer de ovario, fibrosis cística (CF), enfermedad pulmonar obstructiva crónica (COPD), fibrosis pulmonar, síndrome de insuficiencia respiratoria de adultos, bronquitis crónica, efisema hereditario, artritis reumatoide, IBD, o asma.
CU2010000032A 2007-08-17 2010-02-17 Depsipéptidos cíclicos CU23943B1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP07114507 2007-08-17
PCT/EP2008/060689 WO2009024527A1 (en) 2007-08-17 2008-08-14 Cyclic depsipeptides

Publications (2)

Publication Number Publication Date
CU20100032A7 CU20100032A7 (es) 2011-10-05
CU23943B1 true CU23943B1 (es) 2013-09-27

Family

ID=38805728

Family Applications (2)

Application Number Title Priority Date Filing Date
CU2010000032A CU23943B1 (es) 2007-08-17 2010-02-17 Depsipéptidos cíclicos
CU2013000063A CU20130063A7 (es) 2007-08-17 2013-05-02 Proceso de producción de depsipéptidos cíclicos

Family Applications After (1)

Application Number Title Priority Date Filing Date
CU2013000063A CU20130063A7 (es) 2007-08-17 2013-05-02 Proceso de producción de depsipéptidos cíclicos

Country Status (30)

Country Link
US (2) US8178650B2 (es)
EP (1) EP2183273B1 (es)
JP (1) JP5520824B2 (es)
KR (2) KR101227231B1 (es)
CN (1) CN103298827B (es)
AR (1) AR068343A1 (es)
AU (1) AU2008290567B2 (es)
BR (1) BRPI0815547B8 (es)
CA (1) CA2696570C (es)
CL (1) CL2008002394A1 (es)
CO (1) CO6260099A2 (es)
CR (1) CR11251A (es)
CU (2) CU23943B1 (es)
EA (1) EA017735B1 (es)
EC (1) ECSP109968A (es)
ES (1) ES2632392T3 (es)
GT (1) GT201000037A (es)
MA (1) MA31701B1 (es)
MX (1) MX2010001849A (es)
MY (1) MY151973A (es)
NZ (1) NZ583284A (es)
PE (2) PE20141199A1 (es)
PL (1) PL2183273T3 (es)
PT (1) PT2183273T (es)
SV (1) SV2010003485A (es)
TN (1) TN2010000074A1 (es)
TW (1) TW200922613A (es)
UA (1) UA98658C2 (es)
WO (1) WO2009024527A1 (es)
ZA (1) ZA201000776B (es)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2183270B1 (en) 2007-08-17 2014-12-17 Novartis AG Use of cyclic depsipeptides to inhibit kallikrein 7
CN103298827B (zh) 2007-08-17 2017-05-31 诺华股份有限公司 环状酯肽
WO2010092109A2 (en) 2009-02-13 2010-08-19 Novartis Ag Nucleic acid molecule of a biosynthetic cluster encoding non ribosomal peptide synthases and uses thereof
US8614289B2 (en) * 2011-04-20 2013-12-24 Novartis Ag Processes for the manufacture of macrocyclic depsipeptides and new intermediates
US8680054B2 (en) * 2011-04-20 2014-03-25 Novartis Ag Suspension type topical formulations comprising cyclic depsipeptide
US9067978B2 (en) * 2012-10-09 2015-06-30 Novartis Ag Solution phase processes for the manufacture of macrocyclic depsipeptides and new intermediates
US8987413B2 (en) 2012-10-09 2015-03-24 Novartis Ag Aldehyde acetal based processes for the manufacture of macrocyclic depsipeptides and new intermediates
EP3097084B1 (en) 2014-01-23 2020-09-30 Sixera Pharma AB New kallikrein 7 inhibitors
WO2015114144A1 (en) * 2014-02-03 2015-08-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment of netherton syndrome
US20170022254A1 (en) 2014-04-08 2017-01-26 Novartis Ag Novel Aldehyde Acetal Based Processes for the Manufacture of Macrocyclic Depsipeptides and New Intermediates
KR101729848B1 (ko) 2015-06-30 2017-04-24 영남대학교 산학협력단 신규한 해양 바실러스속 균주, 이로부터 분리한 화합물 및 상기 화합물의 약제학적 용도
CN106518880B (zh) * 2015-11-04 2018-10-19 衡阳师范学院 激肽释放酶7小分子抑制剂及其制备方法与用途
US20200040103A1 (en) 2018-03-14 2020-02-06 Genentech, Inc. Anti-klk5 antibodies and methods of use
US11643438B2 (en) 2018-07-20 2023-05-09 The Board Of Regents Of The University Of Oklahoma Antimicrobial peptides and methods of use

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3043252C2 (de) 1980-11-15 1982-12-02 Degussa Ag, 6000 Frankfurt Cyclische Acetale von N-Acylglutaminsäure -γ- semialdehyden, Verfahren zu deren Herstellung und ihre Verwendung
US5595756A (en) 1993-12-22 1997-01-21 Inex Pharmaceuticals Corporation Liposomal compositions for enhanced retention of bioactive agents
DE4421113A1 (de) * 1994-06-16 1995-12-21 Biotechnolog Forschung Gmbh Chondramide, Gewinnungsverfahren, Mittel mit Chondramiden und Mischkultur zur Chondramid-Gewinnung
DE19828043A1 (de) 1998-06-24 1999-12-30 Bayer Ag Ektoparasitizide Mittel
JP2000154198A (ja) 1998-11-20 2000-06-06 Nisshin Flour Milling Co Ltd 環状デプシペプチドの固相合成方法及びその中間体
GB0108234D0 (en) 2001-04-02 2001-05-23 Pharma Mar Sa Process for producing trunkamide A compounds
US20040110228A1 (en) 2002-04-01 2004-06-10 Mcalpine Shelli R. Combinatorial organic synthesis of unique biologically active compounds
ES2341545T3 (es) 2003-06-06 2010-06-22 Arexis Ab Uso de compuestos heterociclicos condensados como inhibidores de scce para el tratamiento de enfermedades de la piel.
GB0322140D0 (en) 2003-09-22 2003-10-22 Pfizer Ltd Combinations
WO2005075667A1 (en) * 2004-02-03 2005-08-18 Bayer Healthcare Ag Diagnostics and therapeutics for diseases associated with kallikrein 7 (klk7)
EP1994181A4 (en) * 2006-02-27 2010-05-19 Univ Arizona IDENTIFICATION AND USE OF NOVOPEPTIDES FOR THE TREATMENT OF CANCER
CN103298827B (zh) 2007-08-17 2017-05-31 诺华股份有限公司 环状酯肽
EP2183270B1 (en) * 2007-08-17 2014-12-17 Novartis AG Use of cyclic depsipeptides to inhibit kallikrein 7
US20110112121A1 (en) 2009-07-06 2011-05-12 Joerg Berghausen Pharmaceutical Compositions and Solid Forms
KR101004362B1 (ko) 2010-03-19 2010-12-28 가톨릭대학교 산학협력단 자가 면역 질환 예방 및 치료용 ＴＮＦ－α와 ＴＷＥＡＫ 이중 길항제
US20120064136A1 (en) 2010-09-10 2012-03-15 Nanobio Corporation Anti-aging and wrinkle treatment methods using nanoemulsion compositions
EP2616037A2 (en) 2010-09-14 2013-07-24 Trima - Israel Phramaceutical Products Maabarot Ltd. Foamable topical composition
US8673974B2 (en) 2010-11-16 2014-03-18 Novartis Ag Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors
KR20140003572A (ko) 2011-01-24 2014-01-09 안테리오스, 인코퍼레이티드 나노입자 조성물
EP3689331A1 (en) 2011-01-24 2020-08-05 Anterios, Inc. Nanoparticle compositions, formulations thereof, and uses thereof
US8614289B2 (en) 2011-04-20 2013-12-24 Novartis Ag Processes for the manufacture of macrocyclic depsipeptides and new intermediates
US8680054B2 (en) 2011-04-20 2014-03-25 Novartis Ag Suspension type topical formulations comprising cyclic depsipeptide
US9067978B2 (en) 2012-10-09 2015-06-30 Novartis Ag Solution phase processes for the manufacture of macrocyclic depsipeptides and new intermediates
US8987413B2 (en) 2012-10-09 2015-03-24 Novartis Ag Aldehyde acetal based processes for the manufacture of macrocyclic depsipeptides and new intermediates

Also Published As

Publication number Publication date
PE20141199A1 (es) 2014-09-24
CL2008002394A1 (es) 2009-05-15
GT201000037A (es) 2012-04-30
CA2696570A1 (en) 2009-02-26
TN2010000074A1 (en) 2011-09-26
JP5520824B2 (ja) 2014-06-11
US8178650B2 (en) 2012-05-15
EP2183273A1 (en) 2010-05-12
PE20091007A1 (es) 2009-08-14
ECSP109968A (es) 2010-03-31
AU2008290567A1 (en) 2009-02-26
MY151973A (en) 2014-07-31
NZ583284A (en) 2012-04-27
PT2183273T (pt) 2017-05-22
TW200922613A (en) 2009-06-01
AU2008290567B2 (en) 2011-05-12
EA017735B1 (ru) 2013-02-28
KR20100044893A (ko) 2010-04-30
EP2183273B1 (en) 2017-04-05
US20090156472A1 (en) 2009-06-18
UA98658C2 (uk) 2012-06-11
EA201000329A1 (ru) 2010-08-30
AR068343A1 (es) 2009-11-11
MA31701B1 (fr) 2010-09-01
SV2010003485A (es) 2011-03-23
CN103298827B (zh) 2017-05-31
KR20120123579A (ko) 2012-11-08
BRPI0815547B1 (pt) 2020-09-15
JP2010536731A (ja) 2010-12-02
CU20100032A7 (es) 2011-10-05
US20120196790A1 (en) 2012-08-02
CN103298827A (zh) 2013-09-11
CA2696570C (en) 2020-12-29
BRPI0815547B8 (pt) 2021-05-25
MX2010001849A (es) 2010-03-10
CU20130063A7 (es) 2013-06-28
ZA201000776B (en) 2010-10-27
KR101227231B1 (ko) 2013-01-28
PL2183273T3 (pl) 2017-09-29
WO2009024527A1 (en) 2009-02-26
US9127044B2 (en) 2015-09-08
BRPI0815547A2 (pt) 2015-02-10
CO6260099A2 (es) 2011-03-22
ES2632392T3 (es) 2017-09-12
CR11251A (es) 2010-03-08

Similar Documents

Publication Publication Date Title
CU23943B1 (es) Depsipéptidos cíclicos
JP2014505733A5 (es)
WO2012143796A3 (en) Anti-inflammation compounds
GT201300121A (es) Derivados de 2,3-dihidroimidazo(1,2-c)quinazolina sustituidos con aminoalcoholes que son de utilidad para tratar trastornos hiperproliferativos y enfermedades asociadas a la angiogénesis
BR112012023578A2 (pt) derivado de piridina e pirazina para o tratamento de cf
UY33715A (es) Anticuerpos humanos contra el ligando 1a de tipo tnf humano (tl1a)
EA201691147A1 (ru) Ионные водные композиции
AU2012316912A8 (en) Novel heterocyclic derivatives and their uses
CY1108900T1 (el) Πολυθειωμενα γλυκοζιδια και αλατα αυτων
CL2011000696A1 (es) Particulas inhalables que comprenden una forma anhidra amorfa de tiotropio con un agente estabilizante que es lactosa; composicion farmaceutica; procedimiento para prepararlas que incluye secado por atomizacion; y su uso en asma y epoc
BR112016007536A2 (pt) compostos, composições e utilizações correspondentes, para a prevenção e/ou o tratamento de dislipidemias
HRP20160328T1 (hr) Tritokvalin za uporabu u liječenju cistične fibroze
PE20141048A1 (es) Combinacion que comprende umeclidinio y un corticosteroide
WO2012051339A3 (en) Methods and compositions for treating respiratory conditions using platelet enriched plasma
PE20150171A1 (es) Nueva forma de dosificacion y formulacion de abediterol
CO7170176A2 (es) Nuevo compuesto que tiene la capacidad para inhibir la enzima deshidrogenasa11b-hidroxiesteroide tipo 1(11b-hsd1) o sal farmaceúticamente aceptable del mismo, método para producir el mismo, y composición farmaceútica que contiene el mismo como ingrediente activo
CL2013002629A1 (es) Compuestos derivados de isoxazolidina; composicion y combinacion farmaceutica que los comprende, util para la prevencion y/o el tratamiento de las enfermedades relacionadas con la reduccion en la cantidad, la actividad o el movimiento de las celulas que participan en la inflamacion, enfermedades respiratorias, asma y epoc.
MX342859B (es) Polisacarido de las semillas de tamarindo para usarse en el tratamiento de enfermedades inflamatorias.
BRPI0819976A2 (pt) composto mimético de ácido para a inibição de isoprenil-s-cisteinil metiltransferase, composição compreedendo os mesmos, bem como uso dos ditos compostos.
CO2017002982A2 (es) Compuesto de pirazolotiazol y medicamento que comprende el mismo
Koga et al. Hesperidin blocks varenicline-aggravated atherosclerotic plaque formation in apolipoprotein E knockout mice by downregulating net uptake of oxidized low-density lipoprotein in macrophages
MX2014014818A (es) Composicion farmaceutica para el tratamiento de enfermedades inflamatorias de la piel.
WO2009102997A3 (en) Acetyl mimic compounds for the inhibition of isoprenyl-s-cysteinyl methyltransferase
CR11666A (es) Farmacoforos duales- antagonistas muscarinicos pdea
CL2010000575A1 (es) Uso de alfa-1 antitripsina o sus derivados para el tratamiento del sindrome de fatiga cronica, donde dicha antitripsina es purificada del plasma humano o es producida por tecnologia transgenica o recombinante.

Legal Events

Date Code Title Description
FG Grant of patent