# US 10,478,484 B2 · GNA1870-based vesicle vaccines for broad spectrum protection against diseases caused by Neisseria meningitidis

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- Number: US 10,478,484 B2
- Document ID: US10478484B2
- Status: Granted
- Kind: B2
- Application number: 16/024,145
- Filed: 2018-06-29
- Published: 2018-12-27
- Granted: 2019-11-19
- Earliest claimed: 2005-01-27
- Assignees: Children's Hospital & Research Center at Oakland
- Applicants: Children's Hospital & Research Center at Oakland
- Inventors: Dan M. Granoff; Victor Chen-Hsi Hou
- Web page: https://patentgrep.com/patent/US10478484B2

## CPC

- A61K 39/095: Neisseria
- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 37/04: Immunostimulants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/22: from Neisseriaceae (F)
- A61K 2039/522: {avirulent or attenuated}
- A61K 2039/575: {humoral response}
- Y10S 530/825: 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)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

The present invention generally provides methods and compositions for eliciting an immune response against Neisseria spp. bacteria in a subject, particularly against a Neisseria meningitidis serogroup B strain.

## Claims

### Claim 1

A composition comprising:
isolated antigenic vesicles prepared from a Neisseria meningitidis (N. meningitidis) genetically modified to disrupt production of the endogenous GNA1870 polypeptide so that the endogenous GNA1870 is not present at detectable levels in the isolated antigenic vesicles and to overexpress at least one full length meningococcal GNA1870 polypeptide at a level sufficient to provide for production of the isolated antigenic vesicles that, when administered to a mammalian subject elicit anti-meningococcal GNA1870 polypeptide antibodies,
wherein the overexpressed GNA1870 polypeptide is a meningococcal variant 1, a variant 2 GNA1870 polypeptide, or a variant 3 GNA1870 polypeptide heterologous to the N. meningitidis,
wherein the isolated antigenic vesicles are outer membrane vesicles (OMVs), microvesicles (MVs), or a mixture of the OMVs and the MVs, and
wherein the N. meningitidis is genetically modified to provide for decreased toxic activity of its lipid A relative to its parental unmodified N. meningitidis; and
a pharmaceutically acceptable carrier.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the isolated antigenic vesicles are outer membrane vesicles (OMVs).

### Claim 3 (depends on 1)

The composition of claim 1, wherein the N. meningitidis is genetically modified to provide for expression of the overexpressed meningococcal GNA1870 polypeptide from a heterologous promoter.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the N. meningitidis deficient in its capsular polysaccharide.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the N. meningitidis comprises a mutation in a gene involved in biosynthesis or modification of lipid A of its lipopolysaccharide.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the N. meningitidis is genetically modified to produce at least two different full length meningococcal GNA1870 polypeptides.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the N. meningitidis is H44/76 or NZ98/254.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the overexpressed GNA1870 polypeptide is a full length variant 3 meningococcal GNA1870 polypeptide.

### Claim 9 (depends on 7)

The composition of claim 7, wherein the overexpressed GNA1870 polypeptide is a full length variant 3 meningococcal GNA1870 polypeptide.

### Claim 10

A Neisseria meningitidis (N. meningitidis) genetically modified to disrupt production of the endogenous GNA1870 polypeptide so that the endogenous GNA1870 is not present at detectable levels in antigenic vesicles prepared from the N. meningitidis and to overexpress at least one full length meningococcal GNA1870 polypeptide at a level sufficient to provide for production of the isolated antigenic vesicles that, when administered to a mammalian subject, elicit anti-meningococcal GNA1870 polypeptide antibodies, wherein the overexpressed GNA1870 polypeptide is a meningococcal variant 1, a variant 2, or a variant 3 GNA1870 polypeptide heterologous to the N. meningitidis, and wherein the antigenic vesicles are outer membrane vesicle (OMV), microvesicle (MVs), or a mixture of the OMVs and the MVs.

### Claim 11 (depends on 10)

The N. meningitidis of claim 10, wherein N. meningitidis is H44/76 or NZ98/254.

### Claim 12 (depends on 10)

The N. meningitidis of claim 10, wherein N. meningitidis is genetically modified to provide for decreased toxic activity of its lipid A relative to its parental unmodified N. meningitidis.

### Claim 13 (depends on 10)

The N. meningitidis of claim 10, wherein the overexpressed GNA1870 polypeptide is a full length variant 3 GNA1870 polypeptide.

### Claim 14 (depends on 11)

The N. meningitidis of claim 11, wherein the overexpressed GNA1870 polypeptide is a full length variant 3 GNA1870 polypeptide.

### Claim 15 (depends on 10)

The N. meningitidis of claim 10, wherein the overexpressed GNA1870 polypeptide is a variant 1 GNA1870 polypeptide.