US 11,897,933 B2Granted

Anti-KRAS-G12D T cell receptors

AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services

InventorsEric Tran, Yong-Chen Lu, Anna Pasetto, Paul F. Robbins, Steven A. Rosenberg, Zhili Zheng

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Abstract

Disclosed is an isolated or purified T cell receptor (TCR) having antigenic specificity for mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) presented in the context of an HLA-Cw*0802 molecule. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

Claims35

Dependent claims

An isolated or purified nucleic acid comprising a nucleotide sequence encoding a TCR comprising:

(i) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
15 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
16;
(ii) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
23 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
24;
(iii) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
31 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
32;
(iv) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
39 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
40;
(v) an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO:
15 and an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO:
16;
(vi) an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO:
23 and an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO:
24;
(vii) an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO:
31 and an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO:
32;
or
(viii) an amino acid sequence at least 99% identical to amino acids 21-132 of SEQ ID NO:
39 and an amino acid sequence at least 99% identical to amino acids 22-130 of SEQ ID NO:
40.

22 more elements

An isolated or purified nucleic acid comprising a nucleotide sequence encoding a polypeptide comprising:

(i) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
15 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
16;
(ii) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
23 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
24;
(iii) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
31 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
32;
(iv) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
39 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
40;
(v) an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO:
15 and an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO:
16;
(vi) an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO:
23 and an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO:
24;
(vii) an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO:
31 and an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO:
32;
or
(viii) an amino acid sequence at least 99% identical to amino acids 21-132 of SEQ ID NO:
39 and an amino acid sequence at least 99% identical to amino acids 22-130 of SEQ ID NO:
40.

22 more elements

An isolated or purified nucleic acid comprising a nucleotide sequence encoding a protein comprising a first polypeptide chain and a second polypeptide chain, wherein

(i) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
15 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
16;
(ii) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
23 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
24;
(iii) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
31 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
32;
(iv) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
39 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
40;
(v) the first polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO:
15 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO:
16;
(vi) the first polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO:
23 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO:
24;
(vii) the first polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO:
31 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO:
32;
or
(viii) the first polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 21-132 of SEQ ID NO:
39 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 22-130 of SEQ ID NO:
40.

22 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/345,390Filed 11 Jun 2021 · continuation
Priority: 2 Aug 2016
Published: US 2021/0300988 A130 Sep 2021
Granted: 13 Feb 2024
Term ends: Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07K 14/7051
Immunoglobulin superfamily: t-cell receptor -CD3 complex
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/32
Characterised by the recombinant expression of specific molecules in the cells of the immune system: t-cell receptors [TCR]
A61K 40/4201
Cancer antigens: neoantigens

Family

Application62/369,883Us provisional application · filed 2 Aug 2016
PCT/US2017/044615Parent of this division · filed 31 Jul 2017
Application16/838,395Parent of this continuation · filed 2 Apr 2020
US 10,611,816 B2Parent of this division · filed 7 Apr 2020
US 2021/0300988 A1Pre-grant publication · published 30 Sep 2021
US 11,208,456 B2Parent of this continuation
Application16/321,899Parent of this division
Application16/838,395Parent of this division
US 2019/0177395 A1Published application
US 2020/0247869 A1Published application
US 11,897,933 B2This patent

From the US filing history. Foreign family members aren’t listed.

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