Peptides and combination of peptides for use in immunotherapy against various cancers
US-10314897-B2 · Jun 11, 2019 · US
US2024182876A1 · US · A1
| Field | Value |
|---|---|
| Publication number | US-2024182876-A1 |
| Application number | US-202318485855-A |
| Country | US |
| Kind code | A1 |
| Filing date | Oct 12, 2023 |
| Priority date | Oct 13, 2022 |
| Publication date | Jun 6, 2024 |
| Grant date | — |
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The present invention provides engineered terminal deoxynucleotidyl transferase (TdT) polypeptides useful in template-independent polynucleotide synthesis, as well as compositions, methods of utilizing these engineered polypeptides, and polynucleotides encoding the engineered terminal deoxynucleotidyl transferases.
Opening claim text (preview).
What is claimed is: 1 . An engineered terminal deoxynucleotidyl transferase comprising a polypeptide sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to a reference sequence selected from SEQ ID NO: 2, 8, 12, 16, 24, 36, 54, 268, 648, 660, 882, 1100, 1336, 1348, 1596, 1654, 1830, 1950, 2008, 2254, 2514, 2524, 2638, 2804, 2812, 2956, 3174, 3222, 3670, 3674, 3796, 3870, 3918, 4266, 4442, 4654, 4850, 4856, 4904, 5002, 5028, 5192, 5246, or a functional fragment thereof, and at least one amino acid residue difference relative to the reference sequence. 2 . The engineered terminal deoxynucleotidyl transferase of claim 1 , wherein the polypeptide sequence comprises residue differences relative to the reference sequence of SEQ ID NO: 2 at a set of amino acid positions selected from: 80/121/185/315; 80/121/185/190/289/290/293/313/342/499; 80/121/185/190/289/290/293/313/315/336/342/359/391/414/470/474/499/522/523; 80/121/185/190/244/289/290/293/313/315/317/336/342/359/391/470/474/499/522/523; 80/121/174/185/190/196/244/266/273/284/288/289/290/293/313/315/317/324/336/342/352/359/391/394/3 97/401/419/428/431/462/470/474/499/522/523; 80/106/121/185/190/205/289/290/293/313/315/336/342/359/391/470/474/499/522/523; 80/106/121/185/190/205/289/290/293/313/342/470/474/499/523; 80/106/121/185/190/244/289/290/293/307/342/359/470/474/499; 80/121/131/185/190/205/244/289/290/293/313/315/336/342/359/391/414/470/474/499/522/523; 80/121/131/185/190/205/244/289/290/293/313/336/342/359/391/414/470/474/499/522/523; 80/121/131/185/190/289/290/293/313/342/470/474/499/522/523; 80/121/174/179/185/190/236/244/288/289/290/293/313/315/317/336/342/359/363/391/394/408/426/462/4 70/474/499/522/523; 80/121/174/185/186/190/236/244/273/284/288/289/290/293/313/315/317/336/342/352/359/391/394/395/4 19/428/431/462/470/474/499/522/523; 80/121/174/185/190/193/196/244/273/284/288/289/290/293/297/313/315/317/324/336/342/352/359/376/3 80/391/394/401/415/419/428/431/435/441/462/470/474/499/522/523; 80/121/174/185/190/193/244/273/284/288/289/290/293/297/313/315/317/336/342/352/359/391/394/415/4 19/428/431/462/470/474/499/522/523; 80/121/174/185/190/236/244/273/282/284/288/289/290/293/313/315/317/336/342/352/359/391/394/395/4 19/428/431/462/470/474/499/522/523; 80/121/174/185/190/244/273/284/288/289/290/293/313/315/317/336/342/352/359/391/394/419/428/431/4 62/470/474/499/522/523; 80/121/174/185/190/244/273/284/288/289/290/293/313/315/317/336/342/359/391/394/428/431/462/470/4 74/499/522/523; 80/121/174/185/190/244/284/288/289/290/293/313/315/317/336/342/352/359/391/394/419/428/431/462/4 70/474/499/522/523; 80/121/174/185/190/244/284/288/289/290/293/313/315/317/336/342/352/359/391/394/428/431/462/470/4 74/499/522/523; 80/121/174/185/190/244/284/288/289/290/293/313/315/317/336/342/359/391/394/428/431/462/470/474/4 99/522/523; 80/121/185/190/196/244/289/290/293/313/315/317/336/342/359/391/470/474/499/522/523; 80/121/185/190/201/289/290/293/313/342/470/474/499/522; 80/121/185/190/244/273/289/290/293/313/315/317/336/342/352/359/391/419/435/470/474/499/522/523; 80/121/185/190/244/289/290/293/300/313/315/317/336/342/359/391/470/474/499/522/523; 80/121/185/190/244/289/290/293/313/315/317/336/342/359/380/391/401/419/470/474/499/522/523; 80/121/185/190/244/289/290/293/313/315/317/336/342/359/391/392/470/474/499/522/523; 80/121/185/190/244/289/290/293/313/315/317/336/342/359/391/395/470/474/499/522/523; 80/121/185/190/244/289/290/293/313/336/342/359/391/414/470/474/499/522/523; 80/121/185/190/289/290/293/313/336/342/359/391/470/474/499/522/523; 80/121/190/289/290; 80/185/236/289/293; 121/185/190/213/289/290/293; and 185/289/290/293. 3 . The engineered terminal deoxynucleotidyl transferase of claim 1 , wherein the polypeptide sequence comprises at least one substitution set comprising substitutions as compared to the reference sequence of SEQ ID NO: 36 at amino acid positions selected from: 174/244/273/284/288/315/317/336/352/359/391/394/419/428/431/462/470/474/522/523; 174/244/284/288/315/317/336/359/391/394/428/431/462/470/474/522/523; 244/315/317/336/359/391/470/474/522/523; and 336/359/391/470/474/522/523; and/or any combination thereof. 4 . The engineered terminal deoxynucleotidyl transferase of claim 1 , wherein the polypeptide sequence comprises at least one substitution or substitution set comprising substitutions as compared to the reference sequence of SEQ ID NO: 8 at amino acid positions selected from: 129/196, 173, 183, 186, 193, 195, 196, 263, 266, 268, 281, 282, 297, 300, 303, 316, 318, 320, 324, 343, 360, 392, 395, 397, 411, 415, 417, 421, 454, 456, 477, 481, and 492, and/or any combinations thereof. 5 . The engineered terminal deoxynucleotidyl transferase of claim 1 , wherein the polypeptide sequence comprises at least one substitution or substitution set comprising substitutions as compared to the reference sequence of SEQ ID NO: 16 at amino acid positions selected from: 186, 186/236/318, 186/236/395, 186/282/318, 193/196, 193/196/266/324/376/380, 193/196/297, 193/196/297/324/376/380/401/415/435/441, 193/196/324, 193/196/324/397/401/441, 193/196/376/380, 193/297/324/376/435, 193/297/324/380, 193/297/415, 193/435, 196, 196/266, 196/266/324/397/401, 196/297/324/435, 236/282, 236/282/395, 236/318/481, 266/297/380/397/401, 282, 282/318, 282/481, 297/380/401/441, 297/435, 318/395, 376/401/441, 415, and 435/441, and/or any combinations thereof. 6 . The engineered terminal deoxynucleotidyl transferase of claim 1 , wherein the polypeptide sequence comprises at least one substitution or substitution set comprising substitutions as compared to the reference sequence of SEQ ID NO: 24 at amino acid positions selected from: 12, 13, 14, 17, 18, 20, 21, 22, 23, 24, 26, 27, 29, 30, 31, 33, 34, 35, 37, 41, 53, 57, 58, 61, 92, 94, 97, 101, 102, 103, 104, 105, 106, 107, 108, 124, 126, 133, 135, 137, 138, 139, 140, 141, 142, 144, 145, 147, 149, 150, 152, 153, 154, 155, 156, 156/294, 159, 160, 161, 162, 163, 7/135, 12, 13, 14, 15, 16, 17/131, 18, 20, 23, 24, 25, 26, 27, 28, 29, 31, 32, 33, 34, 35, 44, 45, 46, 57, 65, 77, 85, 89, 93, 94, 97, 101, 102, 103, 105, 106, 108, 109, 110, 119, 123, 124, 126, 130, 131, 132, 133, 134, 135, 137, 138, 139, 149, 150, 153, and 156, and/or any combinations thereof. 7 . The engineered terminal deoxynucleotidyl transferase of claim 1 , wherein the polypeptide sequence comprises at least one substitution or substitution set comprising substitutions as compared to the reference sequence of SEQ ID NO: 268 at amino acid positions selected from: 14/53/300, 14/53/419, 106/300/415/419/456, 140, and 300/395/419, and/or any combinations thereof. 8 . The engineered terminal deoxynucleotidyl transferase of claim 1 , wherein the polypeptide sequence comprises at least one substitution or substitution set comprising substitutions as compared to the reference sequence of SEQ ID NO: 648 at amino acid positions selected from: 12/14/34, 12/14/34/37/94/140/141/145, 12/14/34/37/106/140/142/150/152/153, 12/14/34/37/141/142, 12/14/34/37/142/145, 12/14/34/37/142/161, 12/14/34/37/150, 12/14/34/37/150/153, 12/14/34/140/142, 12/14/34/140/150, 12/14/34/142/150/153, 12/14/92/94, 12/14/94/150/152, 12/14/106/107/141/142, 12/14/106/108/140/141/145/150, 12/14/106/108/152, 12/14/141/142, 12/14/150/152/153, 12/14/153, 12/34/92/140, 12/34/150/152, 12/37/94/141/150/152/153, 12/37/140/141/150/162, 12/161, 14, 14/31/34/37/140/141/145/161/162, 14/34/37, 14/34/37/145, 14/34/37/152, 14/34/94/106/108/141, 14/34/150/153, 14/106, 14/140, 14/141/161, 14/142, 14/142/161/162, 14/153, 14/161, 20/21/24/33/58/104/106/124/155/156, 20/21/33/58/101/104/106/124/155, 20/21/58/104/106/155/156, 20/33/104/106/124/156, 20/58/101/1
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Polynucleotides, e.g. nucleic acids, oligoribonucleotides · CPC title
Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression · CPC title
DNA nucleotidylexotransferase (2.7.7.31), i.e. terminal nucleotidyl transferase · CPC title
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