JPWO2019222281A5 - - Google Patents
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- JPWO2019222281A5 JPWO2019222281A5 JP2020563907A JP2020563907A JPWO2019222281A5 JP WO2019222281 A5 JPWO2019222281 A5 JP WO2019222281A5 JP 2020563907 A JP2020563907 A JP 2020563907A JP 2020563907 A JP2020563907 A JP 2020563907A JP WO2019222281 A5 JPWO2019222281 A5 JP WO2019222281A5
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- Prior art keywords
- lamp
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- lamp construct
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- 230000002009 allergen Effects 0.000 claims description 21
- 102000004169 proteins and genes Human genes 0.000 claims description 16
- 108090000623 proteins and genes Proteins 0.000 claims description 16
- 229920000023 polynucleotide Polymers 0.000 claims description 8
- 239000002157 polynucleotide Substances 0.000 claims description 8
- 102100005918 LAMP1 Human genes 0.000 claims description 7
- 101700048185 LAMP1 Proteins 0.000 claims description 7
- 210000004027 cells Anatomy 0.000 claims description 7
- 230000001086 cytosolic Effects 0.000 claims description 3
- 102100013953 CD164 Human genes 0.000 claims description 2
- 108010029862 Endolyn Proteins 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims description 2
- 102100005969 LAMP2 Human genes 0.000 claims description 2
- 102100005968 LAMP3 Human genes 0.000 claims description 2
- 101700013770 LAMP5 Proteins 0.000 claims description 2
- 102100005964 LAMP5 Human genes 0.000 claims description 2
- 108010009491 Lysosomal-Associated Membrane Protein 2 Proteins 0.000 claims description 2
- 108010009489 Lysosomal-Associated Membrane Protein 3 Proteins 0.000 claims description 2
- -1 Macrosailin Proteins 0.000 claims description 2
- 102100001089 SCARB2 Human genes 0.000 claims description 2
- 101710031649 SCARB2 Proteins 0.000 claims description 2
- 230000002197 limbic Effects 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 8
- 210000003712 Lysosomes Anatomy 0.000 claims 1
- 108010052285 Membrane Proteins Proteins 0.000 claims 1
- 102000018697 Membrane Proteins Human genes 0.000 claims 1
- 230000001868 lysosomic Effects 0.000 claims 1
- 238000002255 vaccination Methods 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 8
- XUJNEKJLAYXESH-REOHCLBHSA-N L-cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 5
- 235000018417 cysteine Nutrition 0.000 description 5
- 201000010099 disease Diseases 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 1
- 230000002132 lysosomal Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 101710044770 sll1951 Proteins 0.000 description 1
Description
具体的には、目的のアレルゲンの提示をＬＡＭＰと組み合わせることにより、次いで、アレルゲンは、アレルゲンがプロセシングされ得、それ由来のペプチドが、主要組織適合性（ＭＨＣ）クラスＩＩ分子に関連して細胞表面に提示される細胞質エンドソーム／リソソーム区画に効率的に輸送される。
特定の実施形態では、例えば、以下が提供される：
（項目１）
改善されたＬＡＭＰ構築物であって、
ａ．ＬＡＭＰタンパク質のシステイン保存断片；および
ｂ．表１／図１４に記載されている少なくとも１つのアレルゲンＸ（配列番号Ｙ）
を含む、改善されたＬＡＭＰ構築物。
（項目２）
ａ．アレルゲンＸ（配列番号Ｙ）が、前記システイン保存断片のＮ末端に配置されているか；
ｂ．アレルゲンＸ（配列番号Ｙ）が、単一のシステイン保存断片のＣ末端に配置されているか；または
ｃ．アレルゲンＸ（配列番号Ｙ）が、２つのシステイン保存断片の間に配置されている、項目１に記載の改善されたＬＡＭＰ構築物。
（項目３）
表１／図１４のアレルゲンＸ（配列番号Ｙ）の少なくとも１つを含み、好ましくは、ＩＬＣ－１、ＩＬＣ－２、ＩＬＣ－３、ＩＬＣ－４、ＩＬＣ－５またはＩＬＣ－６に示されているように構築されている、項目１または項目２のいずれかに記載の改善されたＬＡＭＰ構築物。
（項目４）
各アレルゲンＸ（配列番号Ｙ）がリンカーにより分離されている、項目３に記載の改善されたＬＡＭＰ構築物。
（項目５）
前記リンカーがアミノ酸配列ＧＰＧＰＧまたはＰＭＧＬＰから選択される、項目４に記載の改善されたＬＡＭＰ構築物。
（項目６）
１つを超えるシステイン保存断片を含む、前述の項目のいずれかに記載の改善されたＬＡＭＰ構築物。
（項目７）
前記システイン保存断片がＬＡＭＰタンパク質の相同ドメインを含む、項目１～６のいずれか一項に記載の改善されたＬＡＭＰ構築物。
（項目８）
ＬＡＭＰタンパク質の膜貫通ドメインをさらに含む、項目１～７のいずれか一項に記載の改善されたＬＡＭＰ構築物。
（項目９）
シグナル配列をさらに含む、項目１～８のいずれかに記載の改善されたＬＡＭＰ構築物。
（項目１０）
前記シグナル配列がＬＡＭＰタンパク質に由来する、項目９に記載の改善されたＬＡＭＰ構築物。
（項目１１）
前記ＬＡＭＰタンパク質が、ＬＡＭＰ－１、ＬＡＭＰ２、ＬＡＭＰ－３、ＬＩＭＰ２、Ｍａｃｒｏｓａｉｌｉｎ、Ｅｎｄｏｌｙｎ、ＬＡＭＰ５またはＬＩＭＢＩＣから選択される、項目１～１０のいずれか一項に記載の改善されたＬＡＭＰ構築物。
（項目１２）
前記ＬＡＭＰタンパク質が配列番号１～２５０のいずれか１つから選択され、および／または前記アレルゲンＸが配列番号Ｙのいずれか１つから選択される、項目１１に記載の改善されたＬＡＭＰ構築物。
（項目１３）
前記ＬＡＭＰタンパク質が、配列番号１～１１３と少なくとも約７０％、少なくとも約７５％、少なくとも約８０％、少なくとも約８５％、少なくとも約９０％、少なくとも約９５％、９６％、９７％、９８％もしくは９９％同一であり、および／または前記アレルゲンＸが、配列番号Ｙと少なくとも約７０％、少なくとも約７５％、少なくとも約８０％、少なくとも約８５％、少なくとも約９０％、少なくとも約９５％、９６％、９７％、９８％もしくは９９％同一である、項目１２に記載の改善されたＬＡＭＰ構築物。
（項目１４）
項目１～１３のいずれか一項に記載の改善されたＬＡＭＰ構築物をコードする、ポリヌクレオチド。
（項目１５）
項目１４に記載のポリヌクレオチドを含む、宿主細胞。
（項目１６）
項目１～１３のいずれか一項に記載の改善されたＬＡＭＰ構築物、項目１４に記載のポリヌクレオチドまたは項目１５に記載の宿主細胞を含む、組成物。
（項目１７）
アレルギー反応の処置を必要とする被験体におけるアレルギー反応を処置する方法であって、被験体に、前記疾患または障害を軽減または処置するために十分な量で項目１～１３のいずれか一項に記載の改善されたＬＡＭＰ構築物、項目１４に記載のポリヌクレオチド、項目１５に記載の宿主細胞または項目１６に記載の組成物を投与することを含む、方法。
（項目１８）
プライミング工程および少なくとも１回のブースティング工程を含む、項目１７に記載の方法。
（項目１９）
項目１～１３のいずれか一項に記載の改善されたＬＡＭＰ構築物、項目１４に記載のポリヌクレオチド、項目１５に記載の宿主細胞または項目１６に記載の組成物を前記プライミング工程で使用する、項目１８に記載の方法。
（項目２０）
前記ブースティング工程が、アレルゲンＸ、改善されたＬＡＭＰ構築物、改善されたＬＡＭＰ構築物によりコードされるポリペプチド、または改善されたＬＡＭＰ構築物を含む細胞の投与を含む、項目１８または１９のいずれかに記載の方法。
（項目２１）
プライミングするために使用されるアレルゲンＸが、ブースティングするために使用されるのと同じものである、項目１７～２０のいずれか一項に記載の方法。
（項目２２）
プライミングするために使用されるアレルゲンＸが、ブースティングするために使用される第２のアレルゲンＸと同じタンパク質に由来する、項目１７～２１のいずれか一項に記載の方法。
（項目２３）
１つを超えるアレルゲンＸを使用してプライミングおよび／またはブースティングする、項目１７～２２のいずれか一項に記載の方法。
Specifically, by combining presentation of an allergen of interest with LAMP, the allergen can then be processed and peptides derived therefrom can be converted to cell surface proteins in association with major histocompatibility (MHC) class II molecules. is efficiently transported to the cytoplasmic endosomal/lysosomal compartment where it is presented to
In certain embodiments, for example, the following are provided:
(Item 1)
An improved LAMP construct comprising:
a. a cysteine-conserved fragment of the LAMP protein; and
b. at least one allergen X (SEQ ID NO: Y) listed in Table 1/Figure 14
An improved LAMP construct comprising:
(Item 2)
a. whether allergen X (SEQ ID NO: Y) is located at the N-terminus of said cysteine conserved fragment;
b. allergen X (SEQ ID NO: Y) is located at the C-terminus of a single cysteine conserved fragment; or
c. 2. The improved LAMP construct of item 1, wherein allergen X (SEQ ID NO:Y) is located between two cysteine conserved fragments.
(Item 3)
comprising at least one of allergen X (SEQ ID NO: Y) of Table 1/FIG. 3. The improved LAMP construct of either item 1 or item 2, which is constructed as
(Item 4)
4. The improved LAMP construct of item 3, wherein each allergen X (SEQ ID NO:Y) is separated by a linker.
(Item 5)
5. The improved LAMP construct of item 4, wherein said linker is selected from the amino acid sequences GPGPG or PMGLP.
(Item 6)
An improved LAMP construct according to any of the preceding items comprising more than one cysteine conserved fragment.
(Item 7)
7. The improved LAMP construct of any one of items 1-6, wherein said cysteine conserved fragment comprises a homologous domain of a LAMP protein.
(Item 8)
8. The improved LAMP construct of any one of items 1-7, further comprising the transmembrane domain of the LAMP protein.
(Item 9)
9. An improved LAMP construct according to any of items 1-8, further comprising a signal sequence.
(Item 10)
10. The improved LAMP construct of item 9, wherein said signal sequence is derived from a LAMP protein.
(Item 11)
11. The improved LAMP construct of any one of items 1-10, wherein said LAMP protein is selected from LAMP-1, LAMP2, LAMP-3, LIMP2, Macrosailin, Endolyn, LAMP5 or LIMBIC.
(Item 12)
12. The improved LAMP construct of item 11, wherein said LAMP protein is selected from any one of SEQ ID NOS: 1-250 and/or said allergen X is selected from any one of SEQ ID NO:Y.
(Item 13)
wherein said LAMP protein is at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, 96%, 97%, 98% or 99% identical to and/or said allergen X is at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, 96% with SEQ ID NO:Y , 97%, 98% or 99% identical.
(Item 14)
A polynucleotide encoding an improved LAMP construct according to any one of items 1-13.
(Item 15)
A host cell comprising the polynucleotide of item 14.
(Item 16)
A composition comprising the improved LAMP construct of any one of items 1-13, the polynucleotide of item 14 or the host cell of item 15.
(Item 17)
A method of treating an allergic reaction in a subject in need thereof, comprising administering to the subject any one of items 1-13 in an amount sufficient to alleviate or treat said disease or disorder. A method comprising administering the improved LAMP construct of item 14, the polynucleotide of item 14, the host cell of item 15 or the composition of item 16.
(Item 18)
18. The method of item 17, comprising a priming step and at least one boosting step.
(Item 19)
wherein the improved LAMP construct of any one of items 1-13, the polynucleotide of item 14, the host cell of item 15 or the composition of item 16 is used in said priming step. 18. The method according to 18.
(Item 20)
20. Any of items 18 or 19, wherein said boosting step comprises administration of allergen X, an improved LAMP construct, a polypeptide encoded by an improved LAMP construct, or a cell comprising an improved LAMP construct. the method of.
(Item 21)
21. A method according to any one of items 17-20, wherein the allergen X used for priming is the same as that used for boosting.
(Item 22)
22. A method according to any one of items 17-21, wherein the allergen X used for priming is derived from the same protein as the second allergen X used for boosting.
(Item 23)
23. A method according to any one of items 17-22, wherein more than one allergen X is used for priming and/or boosting.
Claims (25)
前記アレルゲンは、配列番号２２２の残基２２～３７４、配列番号２２３の残基２３～５１４、および／または配列番号２２４のアミノ酸配列を含み、 said allergen comprises residues 22-374 of SEQ ID NO:222, residues 23-514 of SEQ ID NO:223, and/or the amino acid sequence of SEQ ID NO:224;
前記アレルゲンは、前記２つの相同ドメインの間に配置されている、ＬＡＭＰ構築物。 A LAMP construct, wherein said allergen is located between said two homologous domains.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2024001288A JP2024024094A (en) | 2018-05-15 | 2024-01-09 | Improved lamp constructs comprising allergens |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862672005P | 2018-05-15 | 2018-05-15 | |
| US62/672,005 | 2018-05-15 | ||
| US201862672378P | 2018-05-16 | 2018-05-16 | |
| US62/672,378 | 2018-05-16 | ||
| US201862673932P | 2018-05-20 | 2018-05-20 | |
| US62/673,932 | 2018-05-20 | ||
| PCT/US2019/032305 WO2019222281A1 (en) | 2018-05-15 | 2019-05-14 | Improved lamp constructs comprising allergens |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2024001288A Division JP2024024094A (en) | 2018-05-15 | 2024-01-09 | Improved lamp constructs comprising allergens |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2021523185A JP2021523185A (en) | 2021-09-02 |
| JPWO2019222281A5 true JPWO2019222281A5 (en) | 2022-09-01 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2020563907A Withdrawn JP2021523185A (en) | 2018-05-15 | 2019-05-14 | Improved LAMP constructs containing allergens |
| JP2024001288A Pending JP2024024094A (en) | 2018-05-15 | 2024-01-09 | Improved lamp constructs comprising allergens |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2024001288A Pending JP2024024094A (en) | 2018-05-15 | 2024-01-09 | Improved lamp constructs comprising allergens |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20210261647A1 (en) |
| EP (1) | EP3793595A1 (en) |
| JP (2) | JP2021523185A (en) |
| CA (1) | CA3100004A1 (en) |
| WO (1) | WO2019222281A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2023012652A2 (en) * | 2021-08-03 | 2023-02-09 | Ukko Inc. | Hypoallergenic peanut allergens, production and use thereof |
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| JP4588296B2 (en) * | 2001-04-05 | 2010-11-24 | ジョンズ・ホプキンス・ユニバーシティ | Chimera vaccine |
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| JP2020517271A (en) * | 2017-04-22 | 2020-06-18 | イミュノミック セラピューティックス， インコーポレイテッドＩｍｍｕｎｏｍｉｃ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | Improved LAMP construct |
| JP7222915B2 (en) * | 2017-05-02 | 2023-02-15 | イミュノミック セラピューティックス， インコーポレイテッド | Improved LAMP constructs containing cancer antigens |
-
2019
- 2019-05-14 JP JP2020563907A patent/JP2021523185A/en not_active Withdrawn
- 2019-05-14 CA CA3100004A patent/CA3100004A1/en active Pending
- 2019-05-14 EP EP19728214.8A patent/EP3793595A1/en active Pending
- 2019-05-14 WO PCT/US2019/032305 patent/WO2019222281A1/en unknown
- 2019-05-14 US US17/053,784 patent/US20210261647A1/en active Pending
-
2024
- 2024-01-09 JP JP2024001288A patent/JP2024024094A/en active Pending
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