# US 9,561,266 B2 · Target peptides for immunotherapy and diagnostics

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- Number: US 9,561,266 B2
- Document ID: US9561266B2
- Status: Granted
- Kind: B2
- Application number: 14/424,702
- Filed: 2013-09-03
- Published: 2015-08-13
- Granted: 2017-02-07
- Earliest claimed: 2012-08-31
- Assignees: University of Virginia Patent Foundation; The University of Birmingham
- Applicants: U.Va. Licensing & Ventures Group; The University of Birmingham
- Inventors: Donald F. Hunt; Jeffrey Shabanowitz; Stacy A. Malaker; Victor H. Engelhard; Angela Zarling; Kara L. Cummings; Rebecca C. Obeng; Mark Cobbold
- Web page: https://patentgrep.com/patent/US9561266B2

## CPC

- A61K 39/0011: {Cancer antigens}
- A61K 35/15: Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells (presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00)
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 39/001106: {Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4}
- A61K 39/00111: {Hepatocyte growth factor receptor [HGFR or c-met]}
- A61K 39/001113: {CD22, BL-CAM, siglec-2 or sialic acid- binding Ig-related lectin 2}
- A61K 39/001132: {Fibroblast growth factors [FGF]}
- A61K 39/001151: {p53}
- A61K 39/001156: {Tyrosinase and tyrosinase related proteinases [TRP-1 or TRP-2]}
- A61K 39/001157: {Telomerase or TERT [telomerase reverse transcriptase]}
- A61K 39/001162: {Kinases, e.g. Raf or Src}
- A61K 39/001164: {GTPases, e.g. Ras or Rho}
- A61K 39/001166: {Adhesion molecules, e.g. NRCAM, EpCAM or cadherins}
- A61K 39/001181: {Alpha-feto protein}
- A61K 39/001182: {Carcinoembryonic antigen [CEA]}
- A61K 39/001184: {Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE}
- A61K 39/001186: {MAGE}
- A61K 39/001188: {NY-ESO}
- A61K 39/001189: {PRAME}
- A61K 39/00119: {Melanoma antigens}
- A61K 39/001192: {Glycoprotein 100 [Gp100]}
- A61K 39/001193: {Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; PAP or PSGR}
- A61K 39/001194: {Prostate specific antigen [PSA]}
- A61K 39/001195: {Prostate specific membrane antigen [PSMA]}
- A61K 39/001197: {Breakpoint cluster region-abelson tyrosine kinase [BCR-ABL]}
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/19: Dendritic cells
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/4271: {Melanoma antigens}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- G01N 33/57595: {involving intracellular compounds}
- G01N 33/6863: {Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors}
- A61K 2039/55516: {Proteins; Peptides}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/48: Blood cells, e.g. leukemia or lymphoma
- A61K 2239/57: Skin; melanoma
- C07K 2317/31: multispecific
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

A set of target peptides are presented by HLA A*0101, A*0201, A*0301, B*4402, B*2705, B*1402, and B*0702 on the surface of disease cells. They are envisioned to among other things (a) stimulate an immune response to the proliferative disease, e.g., cancer, (b) to function as immunotherapeutics in adoptive T cell therapy or as a vaccine, (c) facilitate antibody recognition of tumor boundaries in surgical pathology samples, (d) act as biomarkers for early detection and/or diagnosis of the disease, and (e) act as targets in the generation antibody-like molecules which recognize the target-peptide/MHC complex.

## Claims

### Claim 1

A composition comprising:
(a) at least one synthetic target peptide, wherein each synthetic target peptide:
(i) is between 8 and 50 amino acids long, and
(ii) comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2164-2167 and 2374; and
(b) a therapeutically effective amount of an adjuvant.

### Claim 2 (depends on 1)

The composition of claim 1, wherein at least one serine residue in at least one of the synthetic target peptides is replaced with a homo-serine.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the composition comprises at least 5 different peptides.

### Claim 4 (depends on 1)

The composition of claim 1, further comprising at least one peptide derived from MelanA (MART-I), gp100 (Pmel 17), tyrosinase, TRP-1, TRP-2, MAGE-1, MAGE-3, BAGE, GAGE-1, GAGE-2, p15(58), CEA, RAGE, NY-ESO (LAGE), SCP-1, Hom/Mel-40, PRAME, p53, H-Ras, HER-2/neu, BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, Epstein Barr virus antigens, EBNA, human papillomavirus (HPV) antigens E6 and E7, TSP-180, MAGE-4, MAGE-5, MAGE-6, p185erbB2, p180erbB-3, c-met, nm-23H1, PSA, TAG-72-4, CA 19-9, CA 72-4, CAM 17.1, NuMa, K-ras, β-Catenin, CDK4, Mum-1, p16, TAGE, PSMA, PSCA, CT7, telomerase, 43-9F, 5T4, 791Tgp72, alpha-fetoprotein, β-HCG, BCA225, BTAA, CA 125, CA 15-3 (CA 27.29\BCAA), CA 195, CA 242, CA-50, CAM43, CD68\KP1, CO-029, FGF-5, G250, Ga733 (EpCAM), HTgp-175, M344, MA-50, MG7-Ag, MOV18, NB/70K, NY-CO-1, RCAS1, SDCCAG16, TA-90 (Mac-2 binding protein\cyclophilin C-associated protein), TAAL6, TAG72, TLP and TPS.

### Claim 5 (depends on 1)

The composition of claim 1, futher comprising an agent selected from the groupconsisting of anti-CTLA-4, vermurafenib, ipilimumab, dacarbazine, IL-2, temozolomide, imatinib, gefitinib, erlotinib, sunitinib, tyrphostins and telatinib.

### Claim 6 (depends on 1)

The composition of claim 1, further comprising darcarbazine, carmustine and tamoxifen.

### Claim 7 (depends on 1)

The composition of claim 1, wherein at least one of the synthetic target peptides is O-GlcNAcylated.

### Claim 8 (depends on 1)

The composition of claim 1, wherein at least one of the synthetic target peptides comprises the amino acid sequence set forth in SEQ ID NO: 2164, wherein the serine at the fourth position in the sequence is O-GlcNAcylated.

### Claim 9 (depends on 1)

The composition of claim 1, wherein at least one of the synthetic target peptides comprises the amino acid sequence set forth in SEQ ID NO: 2165, wherein the threonine at the fifth position in the sequence is O-GlcNAcylated.

### Claim 10 (depends on 1)

The composition of claim 1, wherein at least one of the synthetic target peptides comprises the amino acid sequence set forth in SEQ ID NO: 2166, wherein the arginine at the first position in the sequence is mono-methylated and the threonine at the fifth position in the sequence is O-GlcNAcylated.

### Claim 11 (depends on 1)

The composition of claim 1, wherein at least one of the synthetic target peptides comprises the amino acid sequence set forth in SEQ ID NO: 2167, wherein the arginine at the first position in the sequence is di-methylated and the threonine at the fifth position in the sequence is O-GlcNAcylated.

### Claim 12 (depends on 1)

The composition of claim 1, wherein at least one of the synthetic target peptides comprises the amino acid sequence set forth in SEQ ID NO: 2374, wherein the serine at the fourth position in the sequence is O-GlcNAcylated.

### Claim 13 (depends on 1)

The composition of claim 1, wherein composition has the ability to stimulate a T cell mediated immune response to at least one of the synthetic target peptides.

### Claim 14 (depends on 1)

The composition of claim 1, wherein the adjuvant is selected from the group consisting of montanide ISA-51, QS-21, tetanus helper peptides, GM-CSF, cyclophosamide, bacillus Calmette-Guerin (BCG), corynbacterium parvum, levamisole, azimezone, isoprinisone, dinitrochlorobenezene (DNCB), keyhole limpet hemocyanins (KLH), incomplete Freunds adjuvant, complete Freunds adjuvant, mineral gels, aluminum hydroxide (Alum), lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol, and diphtheria toxin (DT).

### Claim 15

A composition comprising a synthetic target peptide and an adjuvant, wherein the synthetic target peptide is between 8 and 50 amino acids long and comprises the amino acid sequence set forth in SEQ ID NO: 2165.

### Claim 16 (depends on 15)

The composition of claim 15, wherein the threonine at the fifth position of SEQ ID NO: 2165 is O-GlcNAcylated.

### Claim 17 (depends on 15)

The composition of claim 15, wherein the adjuvant is QS-21.

### Claim 18 (depends on 16)

The composition of claim 16, wherein the adjuvant is QS-21.