# US 9,750,795 B2 · Proteins comprising MRSA PBP2a and fragments thereof, nucleic acids encoding the same, and compositions and their use to prevent and treat MRSA infections

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- Number: US 9,750,795 B2
- Document ID: US9750795B2
- Status: Granted
- Kind: B2
- Application number: 14/365,071
- Filed: 2012-12-11
- Published: 2014-11-20
- Granted: 2017-09-05
- Earliest claimed: 2011-12-12
- Assignees: The Trustees of the University of Pennsylvania
- Applicants: The Trustees of the University of Pennsylvania
- Inventors: David B. Weiner; Matthew P. Morrow
- Web page: https://patentgrep.com/patent/US9750795B2

## CPC

- A61K 39/085: Staphylococcus
- A61K 38/20: Interleukins [IL]
- A61K 38/208: {IL-12}
- A61K 38/2086: {IL-13 to IL-16}
- A61P 31/04: Antibacterial agents
- A61P 37/04: Immunostimulants
- C07K 14/31: from Staphylococcus (G)
- C12Q 1/689: for bacteria
- 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)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

Nucleic acid molecules which encode an MRSA PBP2a protein or a fragment thereof which comprises at least 245 amino acid are disclosed. Compositions comprising the nucleic acid molecules are disclosed. Novel proteins which comprise a MRSA PBP2a protein or a fragment thereof which comprises at least 245 amino acid are disclosed are disclosed. Methods of inducing an immune response against MRSA PBP2a are disclosed, as are methods of treating an individual who has been diagnosed with MRSA and methods of preventing MRSA infection in an individual.

## Claims

### Claim 1

A nucleic acid molecule that encodes a Methicillin-resistant Staphylococcus aureus (MRSA) penicillin-binding protein 2a (PBP2a) protein or a fragment thereof which comprises at least 245 amino acid, the nucleic acid molecule comprising:
an optimized nucleic acid sequence that is at least 98% identical to SEQ ID NO:1 and that encodes a consensus protein at least 98% identical to SEQ ID NO:2; or
an optimized nucleic acid sequence that is at least 98% identical to a fragment of SEQ ID NO:1 and that encodes a fragment of a consensus protein at least 98% identical to SEQ ID NO:2, wherein the fragment encodes an immunogenic fragment of a protein that is 98% identical to a fragment of SEQ ID NO:2 comprising at least 245 amino acids.

### Claim 2 (depends on 1)

The nucleic acid molecule of claim 1 comprising a fragment of a nucleic acid sequence that is at least 98% identical to SEQ ID NO:1 and that encodes a protein at least 98% identical to SEQ ID NO:2, wherein the fragment encodes an immunogenic fragment of a protein that is 98% identical to a fragment of SEQ ID NO:2 that comprises at least 245 amino acids.

### Claim 3 (depends on 2)

The nucleic acid molecule of claim 2 comprising a fragment of a nucleic acid sequence that is at least 98% identical to SEQ ID NO:1 and that encodes a protein at least 98% identical to SEQ ID NO:2, wherein the fragment encodes an immunogenic fragment of SEQ ID NO:2 having at least a 245 amino acids.

### Claim 4 (depends on 2)

The nucleic acid molecule of claim 2 wherein the fragment is a fragment of SEQ ID NO:1.

### Claim 5 (depends on 2)

The nucleic acid molecule of claim 2 comprising SEQ ID NO:5.

### Claim 6 (depends on 2)

The nucleic acid molecule of claim 2 comprising SEQ ID NO:3.

### Claim 7 (depends on 2)

The nucleic acid molecule of claim 2 wherein an immunogenic fragment of a protein that is 98% identical to a fragment of SEQ ID NO:2 comprises at least 245 amino acids is free of coding sequences that encode an MRSA PBP2a transmembrane domain.

### Claim 8 (depends on 1)

The nucleic acid molecule of claim 1 comprising a coding sequence that encodes a signal peptide sequence operable linked to the nucleic acid sequence that is at least 98% identical to SEQ ID NO:1 and that encodes a protein at least 98% identical to SEQ ID NO:2; or the fragment of a nucleic acid sequence that is at least 98% identical to SEQ ID NO:1 and that encodes a protein at least 98% identical to SEQ ID NO:2.

### Claim 9 (depends on 8)

The nucleic acid molecule of claim 8 wherein the signal peptide sequence is an IgE signal peptide sequence SEQ ID NO:13.

### Claim 10 (depends on 9)

The nucleic acid molecule of claim 9 comprising sequence SEQ ID NO:11.

### Claim 11 (depends on 9)

The nucleic acid molecule of claim 9 comprising sequence SEQ ID NO:9.

### Claim 12

The nucleic acid molecule of claim comprising a nucleic acid sequence that is at least 98% identical to SEQ ID NO:1 and that encodes a protein at least 98% identical to SEQ ID NO:2.

### Claim 13 (depends on 12)

The nucleic acid molecule of claim 12 comprising a nucleic acid sequence that is at least 98% identical to SEQ ID NO:1 and that encodes SEQ ID NO:2.

### Claim 14 (depends on 12)

The nucleic acid molecule of claim 12 comprising SEQ ID NO:1.

### Claim 15 (depends on 9)

The nucleic acid molecule of claim 9 comprising SEQ ID NO:7.

### Claim 16 (depends on 1)

The nucleic acid molecule of claim 1 wherein the nucleic acid molecule is a plasmid.

### Claim 17 (depends on 1)

The nucleic acid molecule of claim 1 wherein the nucleic acid molecule is an expression vector and sequences encoding said one more proteins are operable linked to regulatory elements.

### Claim 18 (depends on 1)

The nucleic acid molecule of claim 1 wherein the nucleic acid molecule is incorporated into a viral particle.
