NEOANTIGENS AND METHODS OF THEIR USE

• US 20190307868A1
• Filed: 03/31/2017
• Published: 10/10/2019
• Est. Priority Date: 03/31/2016
• Status: Abandoned Application

• Current Assignee: Biontech US Inc. (BioNTech SE)
• Original Assignee: Neon Therapeutics, Inc. (BioNTech SE)
• Inventors: Rooney, Michael Steven
• Application Number:
  US16/094,851
• Publication Number:
  US 20190307868A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2039/804 Blood cells [leukemia, lymphoma]
• CPC Class Codes: A61K 2039/812 Breast
• CPC Class Codes: A61K 2039/82 Colon
• CPC Class Codes: A61K 2039/828 Stomach
• CPC Class Codes: A61K 2039/836 Intestine
• CPC Class Codes: A61K 2039/844 Liver
• CPC Class Codes: A61K 2039/852 Pancreas
• CPC Class Codes: A61K 2039/86 Lung
• CPC Class Codes: A61K 2039/868 kidney
• CPC Class Codes: A61K 2039/876 Skin, melanoma
• CPC Class Codes: A61K 2039/884 prostate
• CPC Class Codes: A61K 2039/892 Reproductive system [uterus, ovaries, cervix, testes]
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001102 Receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: A61K 39/001103 Receptors for growth factors
• CPC Class Codes: A61K 39/001104 Epidermal growth factor receptors [EGFR]
• CPC Class Codes: A61K 39/001106 Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4
• CPC Class Codes: A61K 39/001107 : Fibroblast growth factor receptors [FGFR]
• CPC Class Codes: A61K 39/001108 : Platelet-derived growth factor receptors [PDGFR]
• CPC Class Codes: A61K 39/001134 : Transforming growth factor [TGF]
• CPC Class Codes: A61K 39/001151 : p53
• CPC Class Codes: A61K 39/001152 : Transcription factors, e.g. SOX or c-MYC
• CPC Class Codes: A61K 39/001154 : Enzymes
• CPC Class Codes: A61K 39/001162 : Kinases, e.g. Raf or Src
• CPC Class Codes: A61K 39/001163 : Phosphatases
• CPC Class Codes: A61K 39/001164 : GTPases, e.g. Ras or Rho
• CPC Class Codes: A61K 39/4611 : T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4615 : Dendritic cells
• CPC Class Codes: A61K 39/4622 : Antigen presenting cells
• CPC Class Codes: A61K 39/464401 : Neoantigens
• CPC Class Codes: A61K 45/06 : Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: C07K 14/47 : from mammals
• CPC Class Codes: C07K 14/4748 : Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
• CPC Class Codes: C07K 14/705 : Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 4/12 : from animals; from humans
• CPC Class Codes: C12N 9/00 : Enzymes; Proenzymes; Compositions thereof preparations containing enzymes for cleaning teeth A61K8/66, A61Q11/00; medicinal preparations containing enzymes or proenzymes A61K38/43; enzyme containing detergent compositions C11D; enzymes with nucleic acid structure, e.g. ribozymes, C12N15/113; Processes for preparing, activating, inhibiting, separating or purifying enzymes preparation of malt C12C1/00

Abstract

The field of the present invention relates to immunotherapeutic peptides, peptide binding agents, and their use, for example, in the immunotherapy of cancer.

Claims

1-294. -294. (canceled)

295. A method of treating cancer in a subject in need thereof comprising administering to the subject a pharmaceutical composition comprising:

(i) a recombinant or synthetic HLA-matched neoantigenic peptide or a polynucleotide encoding the recombinant neoantigenic peptide; and

(ii) a pharmaceutically acceptable excipient;

wherein the neoantigenic peptide comprises a tumor-specific neoepitope comprising one or more contiguous mutant amino acids encoded by a frameshift, wherein the tumor-specific neoepitope is encoded by a gene of cancer cells of the subject or expressed by cancer cells of the subject and is not expressed by a gene of non-cancer cells of the subject or is not encoded by a gene of the non-cancer cells, wherein the tumor-specific neoepitope comprises an amino acid sequence represented by;

A_xB_yC_z,

wherein;

x is 0 or at least 1 and each A is an amino acid encoded by the gene of the cancer cells of the subject and the gene of the non-cancer cells of the subject;

B_y is absent;

z is at least 1 and each C represents the one or more contiguous mutant amino acids encoded by the frameshift;

x+y+z is at least 8;

and

the gene encoding the tumor-specific neoepitope is a gene selected from the group consisting of;

(a) APC, wherein C_z comprises one or more contiguous amino acids of

296. The method of claim 295, wherein the gene encoding the tumor-specific neoepitope is GATA3, wherein C_z comprises one or more contiguous amino acids of

297. The method of claim 295, wherein Cz comprises one or more contiguous amino acids of

299. The method of claim 295, wherein the tumor-specific neoepitope binds to a MHC class I molecule with a binding affinity of 500 nM or less.

300. The method of claim 295, wherein the pharmaceutical composition comprises at least two different neoantigenic peptides, wherein the gene encoding the tumor-specific neoepitope of each of the at least two different neoantigenic peptides is GATA3.

301. The method of claim 297, wherein the tumor-specific neoepitope has a sequence of HVLPEPHLAL (SEQ ID NO:

1428), RPLQTHVLPE (SEQ ID NO;

     1429), or VLWTTPPLQH (SEQ ID NO;

     1430).

302. The method of claim 301, wherein the tumor-specific neoepitope has a sequence of VLWTTPPLQH (SEQ ID NO:

1430) and the subject express an MHC molecule encoded by a A03;

01 HLA allele.

303. The method of claim 297, wherein the tumor-specific neoepitope has a sequence of EPHLALQPL (SEQ ID NO:

529) and the subject express an MHC molecule encoded by a B07;

02 or B08;

01 HLA allele.

304. The method of claim 297, wherein the tumor-specific neoepitope has a sequence of FLKAESKIMF (SEQ ID NO:

536) and the subject express an MHC molecule encoded by a B08;

01 HLA allele.

305. The method of claim 297, wherein the tumor-specific neoepitope has a sequence of IMKPKRDGYM (SEQ ID NO:

550) and the subject express an MHC molecule encoded by a B08;

01 HLA allele.

306. The method of claim 297, wherein the tumor-specific neoepitope has a sequence of LHFCRSSIM (SEQ ID NO:

556) and the subject express an MHC molecule encoded by a B08;

01 HLA allele.

307. The method of claim 297, wherein the tumor-specific neoepitope has a sequence of MFATLQRSSL (SEQ ID NO:

567) and the subject express an MHC molecule encoded by a B07;

02 or B08;

01 HLA allele.

308. The method of claim 297, wherein the tumor-specific neoepitope has a sequence of MFLKAESKI (SEQ ID NO:

568) and the subject express an MHC molecule encoded by a A24;

02 HLA allele.

309. The method of claim 297, wherein the tumor-specific neoepitope has a sequence of VLPEPHLAL (SEQ ID NO:

594) and the subject express an MHC molecule encoded by a A02.01 HLA allele.

310. The method of claim 297, wherein the tumor-specific neoepitope has a sequence of YMFLKAESKI (SEQ ID NO:

598) and the subject express an MHC molecule encoded by a A24;

02 or HLA allele.

311. The method of claim 296, wherein the tumor-specific neoepitope has a sequence of APSESPCSPF (SEQ ID NO:

1431), CPLDHTTPPA (SEQ ID NO;

     1432), FLQEQYHEA (SEQ ID NO;

     1433), RLAFLQEQYH (SEQ ID NO;

     1434), SPCSPFRLAF (SEQ ID NO;

     1435) or SPPWVRALL (SEQ ID NO;

     1436).

312. The method of claim 295, wherein the cancer is breast cancer.

313. The method of claim 312, wherein the breast cancer is selected from the group consisting of metastatic breast cancer, breast invasive carcinoma, luminal NS carcinoma of breast, HER-2-positive breast cancer and MSI+ breast cancer.

314. The method of claim 295, wherein the pharmaceutical composition further comprises an adjuvant.

315. The method of claim 295, wherein the method further comprises administering an immune checkpoint inhibitor.

298. (canceled)