JPWO2021207606A5 - - Google Patents
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- JPWO2021207606A5 JPWO2021207606A5 JP2022561484A JP2022561484A JPWO2021207606A5 JP WO2021207606 A5 JPWO2021207606 A5 JP WO2021207606A5 JP 2022561484 A JP2022561484 A JP 2022561484A JP 2022561484 A JP2022561484 A JP 2022561484A JP WO2021207606 A5 JPWO2021207606 A5 JP WO2021207606A5
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- 241001678559 COVID-19 virus Species 0.000 claims description 25
- 150000001875 compounds Chemical class 0.000 claims description 24
- 230000037430 deletion Effects 0.000 claims description 8
- 238000012217 deletion Methods 0.000 claims description 8
- 230000035772 mutation Effects 0.000 claims description 8
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 claims description 8
- 229960003081 probenecid Drugs 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 229940096437 Protein S Drugs 0.000 claims description 6
- 101710198474 Spike protein Proteins 0.000 claims description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 4
- 239000004138 Stearyl citrate Substances 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 206010016256 fatigue Diseases 0.000 claims description 4
- 239000002207 metabolite Substances 0.000 claims description 4
- 150000007523 nucleic acids Chemical group 0.000 claims description 4
- 208000024891 symptom Diseases 0.000 claims description 4
- 206010002653 Anosmia Diseases 0.000 claims description 2
- 208000025721 COVID-19 Diseases 0.000 claims description 2
- 206010008469 Chest discomfort Diseases 0.000 claims description 2
- 206010011224 Cough Diseases 0.000 claims description 2
- 206010012735 Diarrhoea Diseases 0.000 claims description 2
- 208000000059 Dyspnea Diseases 0.000 claims description 2
- 206010013975 Dyspnoeas Diseases 0.000 claims description 2
- 208000010201 Exanthema Diseases 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims description 2
- 208000000112 Myalgia Diseases 0.000 claims description 2
- 206010028813 Nausea Diseases 0.000 claims description 2
- 206010068319 Oropharyngeal pain Diseases 0.000 claims description 2
- 201000007100 Pharyngitis Diseases 0.000 claims description 2
- 206010037368 Pulmonary congestion Diseases 0.000 claims description 2
- 206010037660 Pyrexia Diseases 0.000 claims description 2
- 208000037656 Respiratory Sounds Diseases 0.000 claims description 2
- 206010040742 Sinus congestion Diseases 0.000 claims description 2
- 206010047924 Wheezing Diseases 0.000 claims description 2
- 235000019558 anosmia Nutrition 0.000 claims description 2
- 208000027499 body ache Diseases 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 201000005884 exanthem Diseases 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 210000002850 nasal mucosa Anatomy 0.000 claims description 2
- 230000008693 nausea Effects 0.000 claims description 2
- 210000001331 nose Anatomy 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 206010037844 rash Diseases 0.000 claims description 2
- 208000013220 shortness of breath Diseases 0.000 claims description 2
- 231100000046 skin rash Toxicity 0.000 claims description 2
- 206010041232 sneezing Diseases 0.000 claims description 2
- 230000029812 viral genome replication Effects 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 38
- 238000000034 method Methods 0.000 description 32
- 241000315672 SARS coronavirus Species 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
Description
当業者は、本明細書に記載される本発明の特定の実施形態に対する多くの均等物を認識するか、または単に日常的な実験だけを使用して確認することができる。そのような均等物は、以下の特許請求の範囲に包含されることが意図されている。
特定の実施形態では、例えば、以下が提供される：
（項目１）
重症急性呼吸器症候群コロナウイルス（ＳＡＲＳ－ＣｏＶ－２）感染の対象を処置する方法であって、前記処置を必要とする対象に、有効量のプロベネシド、その代謝産物、その類似体、および前記のいずれかの薬学的に許容され得る塩から選択される化合物を投与することを含む、方法。
（項目２）
前記対象が、前記ＳＡＲＳ－ＣｏＶ－２に関連する疾患、障害または疾病のうちの１つまたは複数の症状を有する、項目１に記載の方法。
（項目３）
前記１つまたは複数の症状が、発熱、副鼻腔および／または肺のうっ血、鼻水または鼻詰まり、咳、くしゃみ、喉の痛み、身体の痛み、疲労、息切れ、胸部圧迫感、呼気のときの喘鳴、悪寒、筋肉痛、頭痛、下痢、倦怠、悪心、無嗅覚症、皮膚発疹およびそれらの組み合わせから選択される、項目２に記載の方法。
（項目４）
前記対象がＣＯＶＩＤ－１９を有する、項目１に記載の方法。
（項目５）
前記対象が無症候性である、項目１に記載の方法。
（項目６）
前記ＳＡＲＳ－ＣｏＶ－２が、配列番号１または２と少なくとも８５％、８６％、８７％、８８％、８９％、９０％、９１％、９２％、９３％、９４％、９５％、９６％、９７％、９８％、９９％または１００％の配列同一性を含む核酸配列によってコードされるゲノムを含む、項目１に記載の方法。
（項目７）
前記ＳＡＲＳ－ＣｏＶ－２が、配列番号５と少なくとも７０％、７５％、８０％、８５％、８６％、８７％、８８％、８９％、９０％、９１％、９２％、９３％、９４％、９５％、９６％、９７％、９８％、９９％または１００％の配列同一性を含むスパイクタンパク質を含む、項目１に記載の方法。
（項目８）
前記ＳＡＲ－ＣｏＶ－２が、Ｈ６９、場合によりその欠失；Ｖ７０、場合によりその欠失；Ｇ１４２、場合によりＧ１４２Ｄ；Ｋ４１７、場合によりＫ４１７ＮまたはＫ４１７Ｔ；Ｅ４８４、場合によりＥ４８４Ｋ；Ｆ４８６、場合によりＦ４８６Ｌ；およびＮ５０１変異、場合によりＮ５０１ＹまたはＮ５０１Ｔから選択される配列番号５に対して１つまたは複数のスパイクタンパク質変異を含む、項目１に記載の方法。
（項目９）
前記ＳＡＲＳ－ＣｏＶ－２が、Ｂ．１．１．７、Ｂ．１．３５１、Ｐ．１、Ｂ．１．１．２０７、Ｂ．１．４２９、Ｂ．１．４２７またはＢ．１．５２５系統に由来する、項目１に記載の方法。
（項目１０）
前記化合物がプロベネシドまたはその薬学的に許容され得る塩である、項目１に記載の方法。
（項目１１）
重症急性呼吸器症候群コロナウイルス（ＳＡＲＳ－ＣｏＶ－２）感染を予防する方法であって、前記予防を必要とする対象に、有効量のプロベネシド、その代謝産物、その類似体、および前記のいずれかの薬学的に許容され得る塩から選択される化合物を投与することを含む、方法。
（項目１２）
前記対象が前記ＳＡＲＳ－ＣｏＶ－２に曝露されている、項目１１に記載の方法。
（項目１３）
前記対象がＳＡＲＳ－ＣｏＶ－２感染者と密接に接触していた、項目１１に記載の方法。
（項目１４）
前記ＳＡＲＳ－ＣｏＶ－２が、配列番号１または２と少なくとも８５％、８６％、８７％、８８％、８９％、９０％、９１％、９２％、９３％、９４％、９５％、９６％、９７％、９８％、９９％または１００％の配列同一性を含む核酸配列によってコードされるゲノムを含む、項目１１に記載の方法。
（項目１５）
前記ＳＡＲＳ－ＣｏＶ－２が、配列番号５と少なくとも７０％、７５％、８０％、８５％、８６％、８７％、８８％、８９％、９０％、９１％、９２％、９３％、９４％、９５％、９６％、９７％、９８％、９９％または１００％の配列同一性を含むスパイクタンパク質を含む、項目１１に記載の方法。
（項目１６）
前記ＳＡＲ－ＣｏＶ－２が、Ｈ６９、場合によりその欠失；Ｖ７０、場合によりその欠失；Ｇ１４２、場合によりＧ１４２Ｄ；Ｋ４１７、場合によりＫ４１７ＮまたはＫ４１７Ｔ；Ｅ４８４、場合によりＥ４８４Ｋ；Ｆ４８６、場合によりＦ４８６Ｌ；およびＮ５０１変異、場合によりＮ５０１ＹまたはＮ５０１Ｔから選択される配列番号５に対して１つまたは複数の（sphmore）変異を含む、項目１１に記載の方法。
（項目１７）
前記ＳＡＲＳ－ＣｏＶ－２が、Ｂ．１．１．７、Ｂ．１．３５１、Ｐ．１、Ｂ．１．１．２０７、Ｂ．１．４２９、Ｂ．１．４２７またはＢ．１．５２５系統に由来する、項目１１に記載の方法。
（項目１８）
前記化合物がプロベネシドまたはその薬学的に許容され得る塩である、項目１１に記載の方法。
（項目１９）
化合物が、薬学的に許容され得る担体および／または賦形剤をさらに含む医薬組成物中にある、項目１から１８までのいずれか１項に記載の方法。
（項目２０）
前記化合物を全身投与する、項目１から１８までのいずれか１項に記載の方法。
（項目２１）
前記化合物を、経口投与、非経口投与、局所投与または粘膜投与する、項目１から１８までのいずれか１項に記載の方法。
（項目２２）
前記化合物を、肺、鼻粘膜またはそれらの組み合わせに粘膜投与する、項目１から１８までのいずれか１項に記載の方法。
（項目２３）
前記化合物を、ウイルス複製を減少させるのに有効な量で投与する、項目１から１８までのいずれか１項に記載の方法。
（項目２４）
前記化合物が、１０ｍｇ～１，０００ｍｇまたは５０ｍｇ～５００ｍｇの投与量で、必要に応じて毎日２回、必要に応じて１４日間である、項目１から１８までのいずれか１項に記載の方法。
（項目２５）
前記対象をパルス投与によって処置する、項目１から１８までのいずれか１項に記載の方法。
（項目２６）
前記パルス投与が、１，０００ｍｇ～５，０００ｍｇの前記化合物の１回～５回のボーラス投与を含む、項目２５に記載の方法。
（項目２７）
前記ボーラス投与の後に休薬日が続く、項目２６に記載の方法。
（項目２８）
前記化合物を経口で、または注入によって投与する、項目１から１８までのいずれか１項に記載の方法。
（項目２９）
前記対象がヒトである、項目１から１８までのいずれか１項に記載の方法。
（項目３０）
前記化合物を２５０ｍｇ～１，０００ｍｇの用量で１日１回または２回投与する、項目１から１８までのいずれか１項に記載の方法。
（項目３１）
化合物を５００ｍｇの用量で１日２回投与する、項目１から１８までのいずれか１項に記載の方法。
（項目３２）
化合物を２週間またはそれを超えて前記対象に投与する、項目１から１８までのいずれか１項に記載の方法。
Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the scope of the following claims.
In certain embodiments, for example, the following are provided:
(Item 1)
1. A method of treating a subject infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprising administering to a subject in need of said treatment an effective amount of a compound selected from probenecid, its metabolites, its analogs, and pharma- ceutically acceptable salts of any of the foregoing.
(Item 2)
2. The method of claim 1, wherein the subject has one or more symptoms of a disease, disorder, or condition associated with SARS-CoV-2.
(Item 3)
3. The method of claim 2, wherein the one or more symptoms are selected from fever, sinus and/or pulmonary congestion, runny or stuffy nose, coughing, sneezing, sore throat, body aches, fatigue, shortness of breath, chest tightness, wheezing on expiration, chills, muscle aches, headache, diarrhea, fatigue, nausea, anosmia, skin rash and combinations thereof.
(Item 4)
2. The method of claim 1, wherein the subject has COVID-19.
(Item 5)
2. The method of claim 1, wherein the subject is asymptomatic.
(Item 6)
2. The method of claim 1, wherein the SARS-CoV-2 comprises a genome encoded by a nucleic acid sequence comprising at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO:1 or 2.
(Item 7)
2. The method of claim 1, wherein the SARS-CoV-2 comprises a spike protein that comprises at least 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO:5.
(Item 8)
2. The method of claim 1, wherein the SAR-CoV-2 comprises one or more spike protein mutations relative to SEQ ID NO:5 selected from H69, optionally a deletion thereof; V70, optionally a deletion thereof; G142, optionally G142D; K417, optionally K417N or K417T; E484, optionally E484K; F486, optionally F486L; and an N501 mutation, optionally N501Y or N501T.
(Item 9)
2. The method of claim 1, wherein the SARS-CoV-2 is from the B.1.1.7, B.1.351, P.1, B.1.1.207, B.1.429, B.1.427 or B.1.525 lineage.
(Item 10)
2. The method of claim 1, wherein the compound is probenecid or a pharma- ceutically acceptable salt thereof.
(Item 11)
1. A method for preventing Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection, comprising administering to a subject in need of said prevention an effective amount of a compound selected from probenecid, its metabolites, its analogs, and pharma- ceutically acceptable salts of any of the foregoing.
(Item 12)
12. The method of claim 11, wherein the subject has been exposed to SARS-CoV-2.
(Item 13)
12. The method of claim 11, wherein the subject has been in close contact with a SARS-CoV-2 infected individual.
(Item 14)
12. The method of claim 11, wherein the SARS-CoV-2 comprises a genome encoded by a nucleic acid sequence comprising at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO:1 or 2.
(Item 15)
12. The method of claim 11, wherein the SARS-CoV-2 comprises a spike protein that comprises at least 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO:5.
(Item 16)
12. The method of claim 11, wherein the SAR-CoV-2 comprises one or more sphmore mutations relative to SEQ ID NO:5 selected from H69, optionally a deletion thereof; V70, optionally a deletion thereof; G142, optionally G142D; K417, optionally K417N or K417T; E484, optionally E484K; F486, optionally F486L; and a N501 mutation, optionally N501Y or N501T.
(Item 17)
12. The method of claim 11, wherein the SARS-CoV-2 is from the B.1.1.7, B.1.351, P.1, B.1.1.207, B.1.429, B.1.427 or B.1.525 lineage.
(Item 18)
12. The method of claim 11, wherein the compound is probenecid or a pharma- ceutically acceptable salt thereof.
(Item 19)
19. The method according to any one of items 1 to 18, wherein the compound is in a pharmaceutical composition further comprising a pharma- ceutically acceptable carrier and/or excipient.
(Item 20)
20. The method of any one of items 1 to 18, wherein the compound is administered systemically.
(Item 21)
19. The method of any one of items 1 to 18, wherein the compound is administered orally, parenterally, topically or mucosally.
(Item 22)
19. The method of any one of items 1 to 18, wherein the compound is administered mucosally to the lungs, nasal mucosa, or a combination thereof.
(Item 23)
19. The method of any one of items 1 to 18, wherein the compound is administered in an amount effective to reduce viral replication.
(Item 24)
19. The method of any one of items 1 to 18, wherein the compound is administered in a dosage of 10 mg to 1,000 mg or 50 mg to 500 mg, twice daily as needed, for 14 days as needed.
(Item 25)
20. The method of any one of items 1 to 18, wherein the subject is treated by pulse dosing.
(Item 26)
26. The method of claim 25, wherein said pulse administration comprises 1 to 5 bolus administrations of 1,000 mg to 5,000 mg of said compound.
(Item 27)
27. The method of claim 26, wherein the bolus administration is followed by a drug holiday.
(Item 28)
19. The method of any one of items 1 to 18, wherein the compound is administered orally or by injection.
(Item 29)
19. The method of any one of items 1 to 18, wherein the subject is a human.
(Item 30)
19. The method of any one of items 1 to 18, wherein the compound is administered at a dose of 250 mg to 1,000 mg once or twice daily.
(Item 31)
19. The method of any one of items 1 to 18, wherein the compound is administered at a dose of 500 mg twice daily.
(Item 32)
19. The method of any one of items 1 to 18, wherein the compound is administered to the subject for two weeks or more.
Claims (32)
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063008624P | 2020-04-10 | 2020-04-10 | |
| US63/008,624 | 2020-04-10 | ||
| US202063023021P | 2020-05-11 | 2020-05-11 | |
| US63/023,021 | 2020-05-11 | ||
| US16/875,487 US11116737B1 (en) | 2020-04-10 | 2020-05-15 | Methods of using probenecid for treatment of coronavirus infections |
| US16/875,487 | 2020-05-15 | ||
| EP20202059.0 | 2020-10-15 | ||
| EP20202059.0A EP3892269B1 (en) | 2020-04-10 | 2020-10-15 | Probenecid for treating coronavirus infections |
| US202163151551P | 2021-02-19 | 2021-02-19 | |
| US63/151,551 | 2021-02-19 | ||
| PCT/US2021/026588 WO2021207606A1 (en) | 2020-04-10 | 2021-04-09 | Methods for treatment of coronavirus infections |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2023520929A JP2023520929A (en) | 2023-05-22 |
| JPWO2021207606A5 true JPWO2021207606A5 (en) | 2024-04-16 |
Family
ID=78023981
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022561484A Pending JP2023520929A (en) | 2020-04-10 | 2021-04-09 | Methods for treatment of coronavirus infection |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP4132503A4 (en) |
| JP (1) | JP2023520929A (en) |
| CN (1) | CN116075298A (en) |
| AU (1) | AU2021254262A1 (en) |
| CA (1) | CA3173187A1 (en) |
| WO (1) | WO2021207606A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20230302031A1 (en) * | 2020-06-02 | 2023-09-28 | Institut Gustave-Roussy | Modulators Of Purinergic Receptors and Related Immune Checkpoint For Treating Acute Respiratory Distress Syndrome |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7320857B2 (en) * | 2003-06-18 | 2008-01-22 | Chinese National Human Genome Center At Shanghai | Characterization of the earliest stages of the severe acute respiratory syndrome (SARS) virus and uses thereof |
| CA2794096A1 (en) * | 2010-04-07 | 2011-10-13 | Celgene Corporation | Methods for treating respiratory viral infection |
| WO2011146527A2 (en) * | 2010-05-17 | 2011-11-24 | Zirus, Inc. | Mammalian genes involved in infection |
| US11554112B2 (en) * | 2018-06-07 | 2023-01-17 | Herum Therapeutics International Limited | Combinations of β-lactam compounds and probenecid and uses thereof |
| CA3112420A1 (en) * | 2018-09-14 | 2020-03-19 | Jiangyin Usun Pharmaceutical Co., Ltd. | New conjugates of montelukast and peptides |
| BR112021024310A2 (en) * | 2019-06-05 | 2022-02-15 | Univ Emory | Peptidomimetics for the treatment of coronavirus and picornavirus infections |
-
2021
- 2021-04-09 CA CA3173187A patent/CA3173187A1/en active Pending
- 2021-04-09 CN CN202180037562.1A patent/CN116075298A/en active Pending
- 2021-04-09 JP JP2022561484A patent/JP2023520929A/en active Pending
- 2021-04-09 EP EP21785329.0A patent/EP4132503A4/en active Pending
- 2021-04-09 WO PCT/US2021/026588 patent/WO2021207606A1/en unknown
- 2021-04-09 AU AU2021254262A patent/AU2021254262A1/en active Pending
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