# US 2010/0166771 A1 · Genes of an Otitis Media Isolate of Nontypeable Haemophilus Influenzae

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- Number: US 2010/0166771 A1
- Document ID: US20100166771A1
- Status: Published application
- Kind: A1
- Application number: 12/646,424
- Filed: 2009-12-23
- Published: 2010-07-01
- Earliest claimed: 2003-03-06
- Assignees: Nationwide Children's Hospital, Inc.; The Board of Regents of the University of Oklahoma
- Inventors: Lauren O. Bakaletz; Robert S. Munson, JR.; David W. Dyer
- Web page: https://patentgrep.com/patent/US20100166771A1

## CPC

- C07K 14/285: from Pasteurellaceae (F), e.g. Haemophilus influenza
- A61P 27/16: Otologicals
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 31/12: Antivirals
- A61P 37/04: Immunostimulants
- C07K 16/1242: {from Pasteurellaceae (F), e.g. Haemophilus influenza}
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12Q 1/689: for bacteria
- G01N 33/56911: {Bacteria}
- 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)
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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
- 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)
- 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)

## Abstract

The invention relates to the polynucleotide sequence of a nontypeable stain of Haemophilus influenzae (NTHi) and polypeptides encoded by the polynucleotides and uses thereof. The invention also relates to NTHi genes which are upregulated during or in response to NTHi infection of the middle ear and/or the nasopharynx.

## Claims

### Claim 1

An isolated polynucleotide comprising the nucleotide sequence of any one of SEQ ID NOS:577-579, SEQ ID NOS: 589-614, SEQ ID NOS: 675-685, SEQ ID NO: 615, SEQ ID NO: 617, SEQ ID NO: 619, SEQ ID NO: 621, SEQ ID NO: 623, SEQ ID NO: 625, SEQ ID NO: 627, SEQ ID NO: 629, SEQ ID NO: 631, SEQ ID NO: 633, SEQ ID NO: 635, SEQ ID NO: 637, SEQ ID NO: 639, SEQ ID NO: 641, SEQ ID NO: 643, SEQ ID NO: 645, SEQ ID NO: 647, SEQ ID NO: 649, SEQ ID NO: 651, SEQ ID NO: 653, SEQ ID NO: 655, SEQ ID NO: 657, SEQ ID NO: 659, SEQ ID NO: 661, SEQ ID NO: 665, SEQ ID NO: 667, SEQ ID NO: 669, 671, SEQ ID NO: 673, SEQ ID NO: 686, SEQ ID NO: 688, SEQ ID NO: 692, SEQ ID NO: 694, SEQ ID NO: 696, SEQ ID NO: 698, SEQ ID NO: 700, SEQ ID NO: 702, SEQ ID NO: 704, SEQ ID NO: 706, SEQ ID NO: 708, SEQ ID NO: 710, SEQ ID NO: 712, SEQ ID NO: 714, SEQ ID NO: 716, SEQ ID NO: 718, SEQ ID NO: 720, SEQ ID NO: 722, SEQ ID NO: 724, SEQ ID NO:726, SEQ ID NO: 728, SEQ ID NO: 730, SEQ ID NO: 732, SEQ ID NO: 734, SEQ ID NO: 736, SEQ ID NO: 738, SEQ ID NO: 740, SEQ ID NO: 742, SEQ ID NO: 744, SEQ ID NO: 746, SEQ ID NO: 748, SEQ ID NO: 750, SEQ ID NO: 752, SEQ ID NO: 754, SEQ ID NO: 756, SEQ ID NO:758, SEQ ID NO:760, SEQ ID NO: 762, SEQ ID NO: 764, SEQ ID NO: 766, SEQ ID NO:768 or SEQ ID NO: 770.

### Claim 2 (depends on 1)

An isolated polypeptide comprising an amino acid sequence encoded by a nucleotide sequence set of claim 1 or a fragment thereof.

### Claim 3

An isolated polypeptide comprising an amino acid sequence of any one of SEQ ID NO: 616, SEQ ID NO: 618, SEQ ID NO: 620, SEQ ID NO: 622, SEQ ID NO: 624, SEQ ID NO: 626, SEQ ID NO: 628, SEQ ID NO: 628, SEQ ID NO: 630, SEQ ID NO: 632, SEQ ID NO: 634, SEQ ID NO: 636, SEQ ID NO: 638, SEQ ID NO: 640, SEQ ID NO: 642, SEQ ID NO: 644, SEQ ID NO: 646, SEQ ID NO: 648, SEQ ID NO: 650, SEQ ID NO: 652, SEQ ID NO: 654, SEQ ID NO: 656, SEQ ID NO: 658, SEQ ID NO: 660, SEQ ID NO: 662, SEQ ID NO: 666, SEQ ID NO: 668, SEQ ID NO: 670, SEQ ID NO: 672, SEQ ID NO: 674, SEQ ID NO: 687, SEQ ID NO: 689, SEQ ID NO: 691, SEQ ID NO: 693, SEQ ID NO: 695, SEQ ID NO: 697, SEQ ID NO: 699, SEQ ID NO: 701, SEQ ID NO: 703, SEQ ID NO: 705, SEQ ID NO: 707, SEQ ID NO: 709, SEQ ID NO: 711, SEQ ID NO: 713, SEQ ID NO:715, SEQ ID NO: 717, SEQ ID NO: 719, SEQ ID NO: 721, SEQ ID NO:723, SEQ ID NO:725, SEQ ID NO:727, SEQ ID NO:729, SEQ ID NO: 731, SEQ ID NO: 733, SEQ ID NO: 735, SEQ ID NO: 737, SEQ ID NO: 739, SEQ ID NO: 741, SEQ ID NO: 743, SEQ ID NO: 745, SEQ ID NO: 747, SEQ ID NO: 749, SEQ ID NO: 751, SEQ ID NO: 753, SEQ ID NO: 755, SEQ ID NO: 757, SEQ ID NO: 759, SEQ ID NO: 761, 763, SEQ ID NO: 765, SEQ ID NO: 767, SEQ ID NO: 769 or SEQ ID NO: 771.

### Claim 4 (depends on 2)

A composition comprising a polypeptide of claim 2 and a pharmaceutically acceptable carrier.

### Claim 5 (depends on 2)

An antibody that specifically binds to a polypeptide of claim 2 or fragment thereof.

### Claim 6 (depends on 5)

A composition comprising an antibody of claim 5 and a pharmaceutically acceptable carrier.

### Claim 7 (depends on 1)

A method for detecting NTHi bacteria in a biological sample comprising
(a) contacting a polynucleotide of claim 1 or a fragment thereof with a biological sample, and
(b) detecting hybridization of the polynucleotide within the sample.

### Claim 8 (depends on 5)

A method for detecting NTHi bacteria in a biological sample comprising:
(a) contacting an antibody of claim 5 with a biological sample, and
(b) detecting binding of the antibody within the sample.

### Claim 9 (depends on 7)

The method of claim 7 wherein the biological sample is selected from the group consisting of serum, sputum, ear fluid, blood, urine, lymphatic fluid, and cerebrospinal fluid.

### Claim 10 (depends on 2)

A method for eliciting an immune response to NTHi bacteria comprising administering an immunogenically effective dose of a polypeptide of claim 2 or a fragment thereof to a patient at risk of NTHi bacterial infection.

### Claim 11 (depends on 2)

A vaccine comprising a polypeptide of claim 2 or a fragment thereof and a pharmaceutically suitable carrier.

### Claim 12 (depends on 2)

A method for preventing NTHi bacterial infection comprising administering a polypeptide of claim 2 that blocks cellular attachment of NTHi bacteria to a patient at risk of NTHi bacterial infection.

### Claim 13 (depends on 5)

A method for preventing NTHi bacterial infection comprising administering an antibody of claim 5 that blocks cellular attachment of NTHi bacteria to a patient at risk of NTHi bacterial infection.

### Claim 14 (depends on 13)

The method of claim 13 wherein the NTHi infection is in the middle ear.

### Claim 15 (depends on 2)

A method of treating or preventing NTHi bacterial infection comprising administering a molecule that inhibits expression or activity of a polypeptide of claim 2 to a patient in need.

### Claim 16 (depends on 15)

The method of claim 15 wherein the NTHi polypeptide comprises the is encoded by an NTHi gene selected from the group consisting of hisB, lppB, sapA, rbsC, pure, rib, arcB, uxuA, licC, ispZ, mukF, glpR, ihfB, cspD, lav, HI1647, HI0094, HI1163, HI0665, HI1292, HI1064, HI1386, HI1462, HI1369, and HI1598.

### Claim 17 (depends on 15)

The method of claim 15 wherein the NTHi polypeptide comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 616, SEQ ID NO: 618, SEQ ID NO: 620, SEQ ID NO: 622, SEQ ID NO: 624, SEQ ID NO: 626, SEQ ID NO: 628, SEQ ID NO: 634, SEQ ID NO: 638, SEQ ID NO: 642, SEQ ID NO: 644, SEQ ID NO: 646, SEQ ID NO: 650, SEQ ID NO: 652, SEQ ID NO: 656, SEQ ID NO: 658, SEQ ID NO: 660, SEQ ID NO: 662, SEQ ID NO: 666, SEQ ID NO: 668, SEQ ID NO: 670, SEQ ID NO:672 and SEQ ID NO: 674.

### Claim 18 (depends on 15)

The method of claim 15 wherein the molecule administered to the patient in need is selected from the group consisting of an antisense oligonucleotide, a small molecule and an antibody.

### Claim at position 19

19-20. (canceled)

### Claim 21 (depends on 15)

The method of claim 15 wherein the NTHi infection is in the middle ear.