IP Library Patent Application 17744354
Patent Application
App. No. 17/744,354

ANTIGEN-BINDING PROTEINS TARGETING SHARED NEOANTIGENS

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Patent No.
US None
App. No.
17/744,354
Abstract

Provided herein are target HLA-PEPTIDE antigens, e.g., HLA-PEPTIDE neoantigens and shared tumor HLA-PEPTIDE antigens, and antigen binding proteins (ABPs) that bind the target HLA-PEPTIDE antigens. Also disclosed are methods for identifying target HLA-PEPTIDE antigens as well as identifying one or more antigen binding proteins that bind a given HLA-PEPTIDE target antigen.

Claims (47)

1 . An antigen binding protein (ABP) that specifically binds to an HLA-PEPTIDE antigen comprising an HLA-restricted peptide complexed with an HLA Class I molecule, wherein the HLA-restricted peptide is located in the peptide binding groove of an α1/α2 heterodimer portion of the HLA Class I molecule, wherein the HLA Class I molecule and the HLA-restricted peptide are each selected from an HLA-PEPTIDE antigen as described in any one of SEQ ID NOs:10,755 to 29,364, and wherein the ABP comprises a T cell receptor (TCR) or antigen-binding fragment thereof.

2 - 3 . (canceled)

4 . The ABP of claim 1 , wherein the HLA-PEPTIDE antigen is selected from the group consisting of:

a. a RAS_G12D MHC Class I antigen comprising HLA-A*11:01 and the restricted peptide VVVGADGVGK;

b. a RAS_G12V MHC Class I antigen comprising HLA-A*11:01 and the restricted peptide VVVGAVGVGK;

c. a RAS_G12C MHC Class I antigen comprising HLA-A*02:01 and the restricted peptide KLVVVGACGV;

d. a CTNNB1_S45P MHC Class I antigen comprising HLA-A*03:01 and the restricted peptide TTAPPLSGK;

e. a RAS_G12D MHC Class I antigen comprising HLA-A*11:01 and the restricted peptide VVGADGVGK;

f. a RAS_G12V MHC Class I antigen comprising HLA-A*11:01 and the restricted peptide VVGAVGVGK;

g. a RAS_G12V MHC Class I antigen comprising HLA-C*01:02 and the restricted peptide AVGVGKSAL;

h. a RAS_G12V MHC Class I antigen comprising HLA-A*03:01 and the restricted peptide VVVGAVGVGK;

i. a TP53_K132N MHC Class I antigen comprising HLA-A*24:02 and the restricted peptide TYSPALNNMF;

j. a CTNNB1_S37Y MHC Class I antigen comprising HLA-A*02:01 and the restricted peptide YLDSGIHYGA;

k. a RAS_G12C MHC Class I antigen comprising HLA-A*03:01 and the restricted peptide VVVGACGVGK;

l. a RAS_G12C MHC Class I antigen comprising HLA-A*11:01 and the restricted peptide VVVGACGVGK;

m. a RAS_G12D MHC Class I antigen comprising HLA-A*03:01 and the restricted peptide VVVGADGVGK;

n. a RAS_Q61H MHC Class I antigen comprising HLA-A*01:01 and the restricted peptide ILDTAGHEEY; and

o. a TP53_R213L MHC Class I antigen comprising A*02:01 and the restricted peptide YLDDRNTFL.

5 - 7 . (canceled)

8 . The ABP of claim 1 , wherein the HLA-restricted peptide comprises a RAS G12 mutation, optionally wherein the G12 mutation is a G12C, a G12D, a G12V, or a G12A mutation.

9 - 50 . (canceled)

51 . An engineered cell expressing a receptor comprising the antigen binding protein of claim 1 .

52 . The engineered cell of claim 51 , wherein the engineered cell is a T cell, optionally wherein the T cell is selected from the group consisting of: a naive T (TN) cell, an effector T cell (TEFF), a memory T cell, a stem cell memory T cell (TSCM), a central memory T cell (TCM), an effector memory T cell (TEM), a terminally differentiated effector memory T cell, a tumor-infiltrating lymphocyte (TIL), an immature T cell, a mature T cell, a helper T cell, a cytotoxic T cell (CTL), a mucosa-associated invariant T (MALT) cell, a regulatory T cell (Treg), a TH1 cell, a TH2 cell, a TH3 cell, a TH17 cell, a TH9 cell, a TH22 cell, a follicular helper T cell, an natural killer T cell (NKT), an alpha-beta T cell, and a gamma-delta T cell.

53 - 55 . (canceled)

56 . The engineered cell of claim 51 , wherein the engineered cell is an autologous cell of a subject.

57 . The engineered cell of claim 56 , wherein the subject is known or suspected to have cancer.

58 - 61 . (canceled)

62 . The engineered cell of claim 56 , wherein the ABP comprises a T cell receptor (TCR) or an antigen-binding portion thereof, and wherein a polynucleotide encoding the T cell receptor (TCR) or antigen-binding portion thereof is inserted in an endogenous TCR locus.

63 . (canceled)

64 . An isolated polynucleotide or set of polynucleotides encoding the ABP of claim 1 or an antigen-binding portion thereof.

65 - 70 . (canceled)

71 . A pharmaceutical composition comprising the antigen binding protein of claim 1 and a pharmaceutically acceptable excipient.

72 . (canceled)

73 . A method of stimulating an immune response in a subject, comprising administering to the subject an antigen binding protein (ABP) that specifically binds to an HLA-PEPTIDE antigen comprising an HLA-restricted peptide complexed with an HLA Class I molecule, wherein the HLA-restricted peptide is located in the peptide binding groove of an α1/α2 heterodimer portion of the HLA Class I molecule, wherein the HLA Class I molecule and the HLA-restricted peptide are each selected from an HLA-PEPTIDE antigen as described in any one of SEQ ID NOs:10,755 to 29,364, and wherein the ABP comprises a T cell receptor (TCR) or antigen-binding fragment thereof, optionally wherein the subject has cancer, optionally wherein the cancer is selected from a solid tumor and a hematological tumor.

74 - 75 . (canceled)

76 . The method of claim 73 , wherein the cancer expresses or is predicted to express an HLA-PEPTIDE antigen or HLA Class I molecule as described in any one of SEQ ID NOs:10,755 to 29,364, and wherein the ABP binds to the HLA-PEPTIDE antigen, optionally wherein the cancer expresses or is predicted to express an HLA-PEPTIDE antigen comprising an HLA-restricted peptide complexed with an HLA Class I molecule, wherein the HLA-restricted peptide is located in the peptide binding groove of an α1/α2 heterodimer portion of the HLA Class I molecule, wherein the HLA Class I molecule and the HLA-restricted peptide are each selected from an HLA-PEPTIDE antigen as described in any one of SEQ ID NOs:10,755 to 29,364, and wherein the ABP binds to the HLA-PEPTIDE antigen.

77 - 154 . (canceled)

155 . The ABP of claim 1 , ABP comprises an alpha-CDR3 amino acid sequence and corresponding beta-CDR3 amino acid sequence selected from the group consisting of the sequences shown in Tables 1C. 2 and 1C. 3.

156 . The ABP of claim 155 , wherein the ABP further comprises an alpha variable (“V”) segment, an alpha joining (“J”) segment, a beta variable (“V”) segment, a beta joining (“J”) segment, optionally a beta diversity (“D”) segment, and optionally a beta constant region selected from the group consisting of the regions shown in Tables 1C. 2 and 1C. 3 corresponding to the alpha-CDR3 amino acid sequence and corresponding beta-CDR3 amino acid sequence.

157 . The ABP of claim 155 , wherein the ABP comprises an alpha variable region and corresponding beta variable region comprising the amino acid sequences selected from the sequences shown in Tables 1A. 2 and 1A. 3 corresponding to the alpha-CDR3 amino acid sequence and corresponding beta-CDR3 amino acid sequence.

158 . An antigen binding protein (ABP) that specifically binds to an HLA-PEPTIDE antigen comprising an HLA-restricted RAS peptide complexed with an HLA Class I molecule, wherein the HLA-restricted peptide is located in the peptide binding groove of an α1/α2 heterodimer portion of the HLA Class I molecule, wherein the HLA-restricted RAS peptide comprises at least one alteration that makes HLA-restricted RAS peptide sequence distinct from the corresponding peptide sequence of a wild-type RAS peptide, and wherein the ABP comprises an alpha-CDR3 amino acid sequence and corresponding beta-CDR3 amino acid sequence selected from the group consisting of the sequences shown in Tables 1C. 2 and 1C. 3.

159 . (canceled)

160 . The ABP of claim 158 , wherein the HLA-PEPTIDE antigen is (a) a RAS_G12C MHC Class I antigen comprising HLA-A*02:01 and the restricted peptide KLVVVGACGV, or (b) a RAS G12V MHC Class I antigen comprising HLA-A*11:01 and the restricted peptide VVGAVGVGK.

161 . The ABP of claim 160 , wherein the ABP comprises an alpha-CDR3 amino acid sequence and corresponding beta-CDR3 amino acid sequence selected from the group consisting of the sequences shown in Table 1C. 2 or Table 1C. 3.

162 . The ABP of claim 161 , wherein the ABP further comprises an alpha variable (“V”) segment, an alpha joining (“J”) segment, a beta variable (“V”) segment, a beta joining (“J”) segment, optionally a beta diversity (“D”) segment, and optionally a beta constant region selected from the group consisting of the regions shown in Table 1C. 2 or Table 1C. 3 corresponding to the alpha-CDR3 amino acid sequence and corresponding beta-CDR3 amino acid sequence.

163 . The ABP of claim 161 , wherein the ABP comprises an alpha variable region and corresponding beta variable region comprising the amino acid sequences selected from the sequences shown in Table 1A. 2 or Table 1A. 3 corresponding to the alpha-CDR3 amino acid sequence and corresponding beta-CDR3 amino acid sequence.

164 - 167 . (canceled)

Assignments (4)
CORRECTIVE ASSIGNMENT TO CORRECT THE ERRONEOUS REFERENCE TO APPLICATION NUMBERS 10847252, 10847253 AND 11183286 TO INSTEAD REFLECT THE PATENT NUMBERS LISTED IN THE RECORDED ASSIGNMENT DOCUMENT PREVIOUSLY RECORDED ON REEL 70760 FRAME 165. ASSIGNOR(S) HEREBY CONFIRMS THE THE ASSIGNMENT. Recorded Apr 25, 2025
From: GRITSTONE BIO, INC.
To: SEATTLE PROJECT CORP.
Reel/Frame 071079/0653 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 7, 2025
From: GRITSTONE BIO, INC.
To: SEATTLE PROJECT CORP.
Reel/Frame 070760/0165 →
CHANGE OF NAME Recorded May 25, 2022
From: GRITSTONE ONCOLOGY, INC.
To: GRITSTONE BIO, INC.
Reel/Frame 060202/0191 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 19, 2022
From: JOOSS, KARIN; NOWICKA, ALEKSANDRA KATARZYNA; JALLOH, ABUBAKAR; YELENSKY, ROMAN; SUN, JAMES XIN; BUSBY, JENNIFER; DAVIS, MATTHEW JOSEPH
To: GRITSTONE ONCOLOGY, INC.
Reel/Frame 059961/0546 →