# US 11,110,158 B2 · Prostate-associated antigens and vaccine-based immunotherapy regimens

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- Number: US 11,110,158 B2
- Document ID: US11110158B2
- Status: Granted
- Kind: B2
- Application number: 16/058,257
- Filed: 2018-08-08
- Published: 2019-02-07
- Granted: 2021-09-07
- Earliest claimed: 2012-05-04
- Assignees: Pfizer Inc.
- Applicants: Pfizer Inc.
- Inventors: Joseph John Binder; Helen Kim Cho; Michael Robert Dermyer; Karin Ute Jooss; Brian Gregory Pierce; Joyce Tsi Tan; Van To Tsai; James Richard Merson
- Web page: https://patentgrep.com/patent/US11110158B2

## CPC

- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/404: Indoles, e.g. pindolol
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- 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 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 13/08: of the prostate
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/3023: {Lung}
- C07K 16/303: {Liver or Pancreas}
- C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate}
- C12N 9/485: {Exopeptidases (3.4.11-3.4.19)}
- C12N 9/6445: {Kallikreins (3.4.21.34; 3.4.21.35)}
- C12Y 304/17021: Glutamate carboxypeptidase II (3.4.17.21)
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES

## Abstract

The present disclosure provides (a) isolated immunogenic PAA polypeptides; (b) isolated nucleic acid molecules encoding immunogenic PAA polypeptides; (c) vaccine compositions comprising an immunogenic PAA polypeptide or an isolated nucleic acid molecule encoding an immunogenic PAA polypeptide; (d) methods relating to uses of the polypeptides, nucleic acid molecules, and compositions; and (e) vaccine-based immunotherapy regimens which involve co-administration of a vaccine in combination with an immune-suppressive-cell inhibitor and an immune-effector-cell enhancer.

## Claims

### Claim 1

A plasmid vector which comprises a multi-antigen construct encoding two different immunogenic polypeptides, wherein each of the immunogenic polypeptides is encoded by a coding nucleotide sequence on the multi-antigen construct, wherein the multi-antigen construct comprises a separator sequence between the two coding nucleotide sequences, wherein one of the two different immunogenic polypeptides is an immunogenic PSMA polypeptide and the other immunogenic polypeptide is an immunogenic PSA polypeptide, and wherein the immunogenic PSA polypeptide consists of an amino acid sequence selected from the group consisting of:
(1) an amino acid sequence consisting of amino acids 27-263 of SEQ ID NO:15;
(2) an amino acid sequence consisting of amino acids 4-240 of SEQ ID NO:17; and
(3) the amino acid sequence of SEQ ID NO:17.

### Claim 2 (depends on 1)

The plasmid vector according to claim 1, wherein the immunogenic PSMA polypeptide consists of an amino acid sequence selected from the group consisting of:
(1) an amino acid sequence consisting of amino acids 15-750 of SEQ ID NO:1;
(2) the amino acid sequence of SEQ ID NO:3;
(3) the amino acid sequence of SEQ ID NO:5;
(4) the amino acid sequence of SEQ ID NO:7;
(5) an amino acid sequence consisting of amino acids 4-739 of SEQ ID NO:9;
(6) an amino acid sequence consisting of amino acids 4-739 of SEQ ID NO:3;
(7) an amino acid sequence consisting of amino acids 4-739 of SEQ ID NO:5;
(8) an amino acid sequence consisting of amino acids 4-739 of SEQ ID NO:7; and
(9) the amino acid sequence of SEQ ID NO:9.

### Claim 3 (depends on 1)

The plasmid vector according to claim 1, wherein the separator sequence is selected from the group consisting of:
(1) a nucleotide sequence encoding a 2A peptide sequence; and
(2) an internal ribosomal entry site (IRES) sequence.

### Claim 4 (depends on 3)

The plasmid vector according to claim 3, wherein the 2A peptide sequence is selected from the group consisting of the 2A-peptide sequence of FMDV, ERAV, PTV1, EMC-B, EMCV, TME-GD7, ERBV, TaV, DrosC, CrPV, ABPV, IFV, Porcine rotavirus, human rotavirus, T brucei TSR1, and T cruzi AP endonuclease.

### Claim 5 (depends on 4)

The plasmid vector according to claim 4, wherein the 2A peptide sequence is selected from the group consisting of a FMDV 2A-peptide sequence and a TAV 2A peptide sequence.

### Claim 6 (depends on 3)

The plasmid vector according to claim 3, wherein the IRES sequence is an EMCV IRES sequence.

### Claim 7 (depends on 1)

The plasmid vector according to claim 1, wherein the nucleotide sequence encoding the immunogenic PSA polypeptide is selected from the group consisting of:
(1) the nucleotide sequence of SEQ ID NO:18;
(2) the nucleotide sequence of SEQ ID NO:20;
(3) a nucleotide sequence consisting of nucleotides 10-720 of SEQ ID NO:18; and
(4) a degenerate variant of any of the nucleotide sequences provided in (1)-(3).

### Claim 8 (depends on 1)

A pharmaceutical composition, comprising the plasmid vector according to claim 1 and a pharmaceutically acceptable excipient.

### Claim 9 (depends on 1)

A method of treatment for prostate cancer in a patient in need thereof, comprising administering to the patient an effective amount of a plasmid vector according to claim 1.

### Claim 10 (depends on 9)

The method according to claim 9, further comprising administering to the patient an effective amount of an immune modulator.

### Claim 11 (depends on 10)

The method according to claim 10, wherein the immune modulator is selected from the group consisting of TNFR agonists, CTLA-4 antagonists, TLR agonists, programmed cell death protein 1 antagonists, programmed cell death protein 1 ligand antagonists.

### Claim 12 (depends on 11)

The method according to claim 11, wherein the immune modulator is a CTLA-4 antagonist.

### Claim 13 (depends on 12)

The method according to claim 12, wherein the CTLA-4 antagonist is an anti-CTLA-4 antibody.

### Claim 14 (depends on 11)

The method according to claim 11, wherein the immune modulator is a TLR agonist.

### Claim 15 (depends on 14)

The method according to claim 14, wherein the TLR agonist is a CpG oligonucleotide.

### Claim 16 (depends on 11)

The method according to claim 11, wherein the immune modulator is sunitinib malate.

### Claim 17 (depends on 11)

The method according to claim 11, wherein the immune modulator PD-L1 antagonist or PD-1 antagonist.