PL2533761T3 - Sposoby i kompozycje do wytwarzania aerozoli - Google Patents
Sposoby i kompozycje do wytwarzania aerozoliInfo
- Publication number
- PL2533761T3 PL2533761T3 PL11705486T PL11705486T PL2533761T3 PL 2533761 T3 PL2533761 T3 PL 2533761T3 PL 11705486 T PL11705486 T PL 11705486T PL 11705486 T PL11705486 T PL 11705486T PL 2533761 T3 PL2533761 T3 PL 2533761T3
- Authority
- PL
- Poland
- Prior art keywords
- aerosols
- compositions
- preparation
- methods
- Prior art date
Links
- 239000000443 aerosol Substances 0.000 title 1
- 239000000203 mixture Substances 0.000 title 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1027—Paramyxoviridae, e.g. respiratory syncytial virus
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Dispersion Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Otolaryngology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30344710P | 2010-02-11 | 2010-02-11 | |
| US201061426610P | 2010-12-23 | 2010-12-23 | |
| PCT/EP2011/052024 WO2011098552A2 (en) | 2010-02-11 | 2011-02-11 | Methods and compositions for the preparation of aerosols |
| EP11705486.6A EP2533761B1 (en) | 2010-02-11 | 2011-02-11 | Methods and compositions for the preparation of aerosols |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL2533761T3 true PL2533761T3 (pl) | 2019-09-30 |
Family
ID=43899571
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL19152522.9T PL3501499T3 (pl) | 2010-02-11 | 2011-02-11 | Sposoby i kompozycje do wytwarzania aerozoli |
| PL11705486T PL2533761T3 (pl) | 2010-02-11 | 2011-02-11 | Sposoby i kompozycje do wytwarzania aerozoli |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL19152522.9T PL3501499T3 (pl) | 2010-02-11 | 2011-02-11 | Sposoby i kompozycje do wytwarzania aerozoli |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US9713589B2 (pl) |
| EP (2) | EP3501499B1 (pl) |
| JP (3) | JP5951508B2 (pl) |
| CN (2) | CN105380904A (pl) |
| AU (1) | AU2011214299B2 (pl) |
| CA (1) | CA2787718C (pl) |
| CY (1) | CY1122634T1 (pl) |
| DK (1) | DK2533761T3 (pl) |
| ES (2) | ES2931330T3 (pl) |
| HK (1) | HK1222128A1 (pl) |
| HR (1) | HRP20191071T1 (pl) |
| HU (1) | HUE044292T2 (pl) |
| LT (1) | LT2533761T (pl) |
| PL (2) | PL3501499T3 (pl) |
| PT (2) | PT2533761T (pl) |
| SI (1) | SI2533761T1 (pl) |
| WO (1) | WO2011098552A2 (pl) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3004707C (en) | 2009-09-02 | 2022-05-31 | Synedgen Inc. | Methods and compositions for disrupting biofilm utilizing chitosan-derivative compounds |
| PT2533761T (pt) | 2010-02-11 | 2019-06-17 | Ablynx Nv | Métodos e composições para a preparação de aerossóis |
| SG10202010355PA (en) | 2010-03-12 | 2020-11-27 | Berg Llc | Intravenous formulations of coenzyme q10 (coq10) and methods of use thereof |
| EA201490047A1 (ru) * | 2011-06-17 | 2014-08-29 | Берг Ллк | Ингаляционные фармацевтические композиции |
| US20150216977A1 (en) * | 2012-09-18 | 2015-08-06 | Adocia | Stable pharmaceutical composition, comprising an aqueous solution of an antibody-derived therapeutically active protein |
| AU2014233055B2 (en) | 2013-03-15 | 2018-08-09 | Board Of Regents, The University Of Texas System | Inhibition of pulmonary fibrosis with nutlin-3a and peptides |
| NL1040254C2 (en) * | 2013-05-17 | 2014-11-24 | Ablynx Nv | Stable formulations of immunoglobulin single variable domains and uses thereof. |
| CA2943376C (en) * | 2014-04-03 | 2022-06-14 | Medizinische Hochschule Hannover | Nebulization of immunoglobulin |
| AU2015314775A1 (en) * | 2014-09-11 | 2017-03-30 | Synedgen, Inc. | Compositions and methods of use thereof |
| SG11201702688UA (en) * | 2014-10-10 | 2017-04-27 | Ablynx Nv | Methods of treating rsv infections |
| TR201909589T4 (tr) * | 2014-10-10 | 2019-07-22 | Ablynx Nv | Solunum hastalıklarının aerosol terapisinde kullanıma yönelik inhalasyon cihazı. |
| EP4056194A1 (en) * | 2015-02-27 | 2022-09-14 | Board of Regents, The University of Texas System | Polypeptide therapeutics and uses thereof |
| EP3452505A1 (en) | 2016-05-02 | 2019-03-13 | Ablynx NV | Treatment of rsv infection |
| WO2018099968A1 (en) | 2016-11-29 | 2018-06-07 | Ablynx N.V. | Treatment of infection by respiratory syncytial virus (rsv) |
| TWI802576B (zh) | 2017-06-02 | 2023-05-21 | 德商馬克專利公司 | 與ａｄａｍｔｓ結合之免疫球蛋白 |
| JP7496826B2 (ja) | 2018-09-10 | 2024-06-07 | ラング セラピューティクス，エルエルシー | Ｃａｖ－１タンパク質の修飾ペプチドフラグメント及び線維症の治療におけるその使用 |
Family Cites Families (62)
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|---|---|---|---|---|
| EP0368684B2 (en) | 1988-11-11 | 2004-09-29 | Medical Research Council | Cloning immunoglobulin variable domain sequences. |
| US5945098A (en) | 1990-02-01 | 1999-08-31 | Baxter International Inc. | Stable intravenously-administrable immune globulin preparation |
| US5938117A (en) | 1991-04-24 | 1999-08-17 | Aerogen, Inc. | Methods and apparatus for dispensing liquids as an atomized spray |
| EP2192131A1 (en) | 1992-08-21 | 2010-06-02 | Vrije Universiteit Brussel | Immunoglobulins devoid of light chains |
| US6838254B1 (en) | 1993-04-29 | 2005-01-04 | Conopco, Inc. | Production of antibodies or (functionalized) fragments thereof derived from heavy chain immunoglobulins of camelidae |
| FR2708622B1 (fr) | 1993-08-02 | 1997-04-18 | Raymond Hamers | Vecteur recombinant contenant une séquence d'un gène de lipoprotéine de structure pour l'expression de séquences de nucléotides. |
| US6205999B1 (en) | 1995-04-05 | 2001-03-27 | Aerogen, Inc. | Methods and apparatus for storing chemical compounds in a portable inhaler |
| US5586550A (en) | 1995-08-31 | 1996-12-24 | Fluid Propulsion Technologies, Inc. | Apparatus and methods for the delivery of therapeutic liquids to the respiratory system |
| US6014970A (en) | 1998-06-11 | 2000-01-18 | Aerogen, Inc. | Methods and apparatus for storing chemical compounds in a portable inhaler |
| US5758637A (en) | 1995-08-31 | 1998-06-02 | Aerogen, Inc. | Liquid dispensing apparatus and methods |
| US6085740A (en) | 1996-02-21 | 2000-07-11 | Aerogen, Inc. | Liquid dispensing apparatus and methods |
| EP0739981A1 (en) | 1995-04-25 | 1996-10-30 | Vrije Universiteit Brussel | Variable fragments of immunoglobulins - use for therapeutic or veterinary purposes |
| DK0937140T3 (da) | 1996-06-27 | 2008-01-28 | Vlaams Interuniv Inst Biotech | Antistofmolekyler, som interagerer specifikt med et målmolekyles aktive sted eller klöft |
| EP1027439B1 (en) | 1997-10-27 | 2010-03-17 | Bac Ip B.V. | Multivalent antigen-binding proteins |
| AU3596599A (en) | 1998-01-26 | 1999-08-09 | Unilever Plc | Method for producing antibody fragments |
| AU3041100A (en) | 1999-01-05 | 2000-07-24 | Unilever Plc | Binding of antibody fragments to solid supports |
| DE60013767T3 (de) | 1999-01-19 | 2009-07-09 | Unilever N.V. | Verfahren zur herstellung von antikörperfragmenten |
| WO2000065057A1 (en) | 1999-04-22 | 2000-11-02 | Unilever Plc | Inhibition of viral infection using monovalent antigen-binding proteins |
| US6479280B1 (en) | 1999-09-24 | 2002-11-12 | Vlaams Interuniversitair Institutuut Voor Biotechnologie Vzw | Recombinant phages capable of entering host cells via specific interaction with an artificial receptor |
| AU1859201A (en) | 1999-11-29 | 2001-06-12 | Unilever Plc | Immobilisation of proteins |
| WO2001044301A1 (en) | 1999-11-29 | 2001-06-21 | Unilever Plc | Immobilized single domain antigen-binding molecules |
| ES2324280T3 (es) | 2000-03-14 | 2009-08-04 | Unilever N.V. | Dominios variables de la cadena pesada de anticuerpos frente a lipasas dieteticas humanas y sus usos. |
| US20030190598A1 (en) | 2000-05-26 | 2003-10-09 | Jasmid Tanha | Single-domain antigen-binding antibody fragments derived from llama antibodies |
| AU2002229639A1 (en) | 2000-12-13 | 2002-06-24 | De Haard, Johannes Joseph Wilhelmus | Camelidae antibody arrays |
| US20060073141A1 (en) | 2001-06-28 | 2006-04-06 | Domantis Limited | Compositions and methods for treating inflammatory disorders |
| US7371849B2 (en) | 2001-09-13 | 2008-05-13 | Institute For Antibodies Co., Ltd. | Methods of constructing camel antibody libraries |
| JP2005289809A (ja) | 2001-10-24 | 2005-10-20 | Vlaams Interuniversitair Inst Voor Biotechnologie Vzw (Vib Vzw) | 突然変異重鎖抗体 |
| AU2002351896A1 (en) | 2001-12-11 | 2003-06-23 | Ablynx N.V. | Method for displaying loops from immunoglobulin domains in different contexts |
| AU2002360068B2 (en) | 2001-12-21 | 2009-09-03 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw | Method for cloning of variable domain sequences |
| CA2471645A1 (en) | 2002-01-03 | 2003-07-10 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw | Immunoconjugates useful for treatment of tumours |
| US20050271660A1 (en) | 2002-09-06 | 2005-12-08 | Alexion Pharmaceuticals, Inc. | Nebulization of monoclonal antibodies for treating pulmonary diseases |
| AU2003286004A1 (en) | 2002-11-08 | 2004-06-07 | Ablynx N.V. | Single domain antibodies directed against interferon- gamma and uses therefor |
| JP2006520584A (ja) | 2002-11-08 | 2006-09-14 | アブリンクス エン．ヴェー． | 安定化単一ドメイン抗体 |
| CN101412759A (zh) | 2003-01-10 | 2009-04-22 | 埃博灵克斯股份有限公司 | 治疗性多肽,其同源物、其片段及其在调节血小板介导的聚集方面的应用 |
| US7461263B2 (en) | 2003-01-23 | 2008-12-02 | Unspam, Llc. | Method and apparatus for a non-revealing do-not-contact list system |
| WO2005018629A1 (en) | 2003-08-12 | 2005-03-03 | Yarbrough William M | Treatment for acne vulgaris and method of use |
| ES2352697T3 (es) | 2003-11-07 | 2011-02-22 | Ablynx N.V. | Anticuerpos de dominio único de camelidae vhh dirigidos contra el receptor del factor de crecimiento epidérmico y usos de los mismos. |
| US7563443B2 (en) | 2004-09-17 | 2009-07-21 | Domantis Limited | Monovalent anti-CD40L antibody polypeptides and compositions thereof |
| CA2583017A1 (en) | 2004-10-13 | 2006-04-20 | Ablynx N.V. | Single domain camelide anti-amyloid beta antibodies and polypeptides comprising the same for the treatment and diagnosis of degenerative neural diseases such as alzheimer's disease |
| CA2595682A1 (en) | 2005-01-31 | 2006-08-03 | Ablynx N.V. | Method for generating variable domain sequences of heavy chain antibodies |
| EP2172484A3 (en) | 2005-05-18 | 2010-05-19 | Ablynx N.V. | Serum albumin binding proteins |
| CN101213214B (zh) | 2005-05-20 | 2014-06-25 | 埃博灵克斯股份有限公司 | 针对冯威勒布兰特因子的单一结构域vhh抗体 |
| WO2007085815A2 (en) * | 2006-01-24 | 2007-08-02 | Domantis Limited | Ligands that bind il-4 and/or il-13 |
| US20110059101A9 (en) | 2006-03-13 | 2011-03-10 | Ablynx N.V. | Amino Acid Sequences Directed Against Il-6 And Polypetides Comprising The Same For The Treatment Of Diseases And Disorders Associated With Il-6 Mediated Signalling |
| AU2007285695B2 (en) | 2006-08-18 | 2012-05-24 | Ablynx N.V. | Amino acid sequences directed against IL-6R and polypeptides comprising the same for the treatment of diseases and disorders associated with IL-6-mediated signalling |
| WO2008028977A2 (en) | 2006-09-08 | 2008-03-13 | Ablynx N.V. | Serum albumin binding proteins with long half-lives |
| EP2081960B1 (en) | 2006-10-27 | 2018-06-27 | Ablynx N.V. | Intranasal delivery of polypeptides and proteins |
| US8907065B2 (en) | 2006-12-15 | 2014-12-09 | Ablynx N.V. | Polypeptides that modulate the interaction between cells of the immune system |
| US20100062004A1 (en) | 2006-12-19 | 2010-03-11 | Ablynx N.V. | Amino acid sequences directed against gpcrs and polypeptides comprising the same for the treatment of gpcr-related diseases and disorders |
| EP2514767A1 (en) | 2006-12-19 | 2012-10-24 | Ablynx N.V. | Amino acid sequences directed against a metalloproteinase from the ADAM family and polypeptides comprising the same for the treatment of ADAM-related diseases and disorders |
| US20100166734A1 (en) | 2006-12-20 | 2010-07-01 | Edward Dolk | Oral delivery of polypeptides |
| WO2008077945A2 (en) | 2006-12-22 | 2008-07-03 | Ablynx N.V. | Anti-chemokine (ccl2, ccl3, ccl5, cxcl11, cxcl12) single-domain antibodies |
| JP5419709B2 (ja) * | 2007-01-09 | 2014-02-19 | ワイス・エルエルシー | 抗ｉｌ−１３抗体製剤およびその使用 |
| AU2008219216A1 (en) | 2007-02-21 | 2008-08-28 | Ablynx N.V. | Amino acid sequences directed against vascular endothelial growth factor and polypeptides comprising the same for the treatment of conditions and diseases characterized by excessive and/or pathological angiogenesis or neovascularization |
| WO2008142165A1 (en) | 2007-05-24 | 2008-11-27 | Ablynx N.V. | Amino acid sequences directed against growth factor receptors and polypeptides comprising the same for the treatment of diseases and disorders associated with growth factors and their receptors |
| CA2687903C (en) | 2007-05-24 | 2016-09-13 | Ablynx N.V. | Amino acid sequences directed against rank-l and polypeptides comprising the same for the treatment of bone diseases and disorders |
| WO2009068625A2 (en) | 2007-11-27 | 2009-06-04 | Ablynx N.V. | Amino acid sequences directed against her2 and polypeptides comprising the same for the treatment of cancers and/or tumors |
| JP2011506396A (ja) | 2007-12-13 | 2011-03-03 | グラクソ グループ リミテッド | 肺送達用組成物 |
| AU2009254501B2 (en) | 2008-06-05 | 2014-07-31 | Ablynx N.V. | Amino acid sequences directed against envelope proteins of a virus and polypeptides comprising the same for the treatment of viral diseases |
| LT2438087T (lt) | 2009-06-05 | 2017-08-25 | Ablynx N.V. | Trivalenčiai nanokūno konstruktai prieš žmogaus respiratorinį sincitinį virusą (hrsv), skirti kvėpavimo takų infekcijų profilaktikai ir (arba) gydymui |
| ES2831323T3 (es) | 2009-09-03 | 2021-06-08 | Ablynx Nv | Formulaciones estables de polipéptidos y usos de las mismas |
| PT2533761T (pt) | 2010-02-11 | 2019-06-17 | Ablynx Nv | Métodos e composições para a preparação de aerossóis |
-
2011
- 2011-02-11 PT PT11705486T patent/PT2533761T/pt unknown
- 2011-02-11 WO PCT/EP2011/052024 patent/WO2011098552A2/en active Application Filing
- 2011-02-11 CA CA2787718A patent/CA2787718C/en active Active
- 2011-02-11 EP EP19152522.9A patent/EP3501499B1/en active Active
- 2011-02-11 AU AU2011214299A patent/AU2011214299B2/en active Active
- 2011-02-11 DK DK11705486.6T patent/DK2533761T3/da active
- 2011-02-11 CN CN201510824525.1A patent/CN105380904A/zh active Pending
- 2011-02-11 SI SI201131740T patent/SI2533761T1/sl unknown
- 2011-02-11 PT PT191525229T patent/PT3501499T/pt unknown
- 2011-02-11 PL PL19152522.9T patent/PL3501499T3/pl unknown
- 2011-02-11 CN CN201180009097.7A patent/CN102753148B/zh active Active
- 2011-02-11 PL PL11705486T patent/PL2533761T3/pl unknown
- 2011-02-11 LT LTEP11705486.6T patent/LT2533761T/lt unknown
- 2011-02-11 HU HUE11705486 patent/HUE044292T2/hu unknown
- 2011-02-11 ES ES19152522T patent/ES2931330T3/es active Active
- 2011-02-11 EP EP11705486.6A patent/EP2533761B1/en active Active
- 2011-02-11 JP JP2012552404A patent/JP5951508B2/ja active Active
- 2011-02-11 US US13/577,961 patent/US9713589B2/en active Active
- 2011-02-11 ES ES11705486T patent/ES2738114T3/es active Active
-
2016
- 2016-06-08 JP JP2016114294A patent/JP6283064B2/ja active Active
- 2016-08-31 HK HK16110367.6A patent/HK1222128A1/zh unknown
-
2017
- 2017-04-24 US US15/495,199 patent/US11007146B2/en active Active
-
2018
- 2018-01-25 JP JP2018010149A patent/JP7019433B2/ja active Active
-
2019
- 2019-06-13 HR HRP20191071TT patent/HRP20191071T1/hr unknown
- 2019-06-26 CY CY20191100668T patent/CY1122634T1/el unknown
-
2021
- 2021-04-19 US US17/233,621 patent/US12083219B2/en active Active
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