# US 10,370,437 B2 · Antibodies that modulate immunity to drug resistant and latent MTB infections

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,370,437 B2
- Document ID: US10370437B2
- Status: Granted
- Kind: B2
- Application number: 15/850,208
- Filed: 2017-12-21
- Published: 2018-05-10
- Granted: 2019-08-06
- Earliest claimed: 2013-08-30
- Assignees: Longhorn Vaccines and Diagnostics, LLC
- Applicants: Longhorn Vaccines and Diagnostics, LLC
- Inventors: Gerald W. Fischer; Luke T. Daum; Richard F. Schuman; Clara J. Sei
- Web page: https://patentgrep.com/patent/US10370437B2

## CPC

- C07K 16/1289: Mycobacteriaceae (F)
- A61K 39/04: Mycobacterium, e.g. Mycobacterium tuberculosis
- A61K 39/12: Viral antigens
- A61K 39/40: bacterial
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/06: for tuberculosis
- A61P 31/16: for influenza or rhinoviruses
- A61K 2039/521: {inactivated (killed)}
- A61K 2039/522: {avirulent or attenuated}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2039/55505: {Inorganic adjuvants}
- A61K 2039/55544: {Bacterial toxins}
- A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59}
- A61K 2039/575: {humoral response}
- A61K 2039/6037: {Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/55: Fab or Fab'
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- 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)
- 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

## Abstract

The invention is directed to compositions and methods for stimulating, enhancing or modulating the immune system of a patient before or after infection by a pathogen, and in particular multidrug resistant (MDR) MTB and extremely drug resistant (XDR) MTB. Compositions of the invention contain non-naturally occurring antigens that generate an effective cellular and/or humoral immune response to MTB and/or antibodies that are specifically reactive to MTB antigens. The greater activity of the immune system generated by a vaccine of the invention increases generation of memory T cells that provide for a greater and/or extended response to an MTB infection. Responses involve an increased generation of antibodies that enhance immunity against MTB infection and promote an enhanced phagocytic response. Monoclonal antibodies produced by the non-naturally occurring antigens enhance phagocytosis and killing of mycobacteria by phagocytic cells, enhance clearance of MTB from the blood and modulate immunity and cytokine responses.

## Claims

### Claim 1

A method for treating infection of drug-resistant Mycobacterium tuberculosis (MTB) in a mammal comprising:
providing an immunological composition containing an antibody that binds to an epitope of an antigen of MTB, wherein the antigen is obtained or derived from MTB that has been killed by exposure to a chemical and/or physical treatment wherein,
the epitope is not immunologically available prior to the chemical and/or physical treatment,
the antigen comprises peptidoglycan, mycolic acid, an MTB heat-shock protein, or lipoarabinomannan, and
the chemical and/or physical treatment comprises exposure to about 70% ethanol or about 2% glutaraldehyde, activated with sodium biocarbonate; and
administering the composition to the mammal,
wherein the composition induces the immunological system of the mammal to promote phagocytosis and killing MTB infected cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein the phagocytosis and killing is enhanced in the presence of the composition as compared to the phagocytosis and killing of mycobacteria in the absence of the composition.

### Claim 3 (depends on 1)

The method of claim 1, wherein the composition comprises polyclonal antibodies, monoclonal antibodies, or both polyclonal and monoclonal antibodies.

### Claim 4 (depends on 2)

The method of claim 2, wherein the epitope is chemically or physically altered as compared with the naturally occurring epitope.

### Claim 5 (depends on 1)

The method of claim 1, wherein the immunological composition is an adjunctive therapy in combination with administration of an antibiotic.

### Claim 6 (depends on 1)

The method of claim 1, wherein administration of the immunological composition clears MTB from the blood of the mammal.

### Claim 7 (depends on 1)

The method of claim 1, wherein the immunological composition modulates immunity to drug-resistant MTB.

### Claim 8 (depends on 1)

The method of claim 1, wherein the immunological composition is administered at a therapeutically-effective dose.

### Claim 9

A method of treating an infection in a mammal caused by a Mycobacterium tuberculosis (MTB) microorganism comprising:
administering a composition to the mammal, wherein the composition contains an antibody that binds to an epitope of an MTB antigen, wherein:
the epitope is immunologically exposed only after the MTB microorganism is exposed to a chemical and/or physical treatment sufficient to kill the microorganism;
the MTB antigen comprises peptidoglycan, mycolic acid, an MTB heat-shock protein or lipoarabinomannan; and
the chemical and/or physical treatment comprises exposure of the MTB microorganism to about 70% ethanol or about 2% glutaraldehyde, activated with sodium bicarbonate, in a manner sufficient to kill the MTB microorganism;
inducing the immunological system of the mammal to promote opsonophagocytosis of cells infected with the MTB microorganism.

### Claim 10

A method of treating an infection caused by a Mycobacterium tuberculosis (MTB) microorganism comprising:
exposing MTB microorganisms to a chemical and/or physical treatment which would be sufficient to kill MTB microorganisms, wherein the chemical and/or physical treatment comprises exposure to about 70% ethanol or about 2% glutaraldehyde, activated with sodium bicarbonate, that immunologically exposes an MTB epitope that is not immunologically exposed with untreated MTB microorganisms;
generating antibodies to the exposed MTB epitope; and
administering the antibodies generated to a mammal with an active or suspected MTB infection, wherein administration induces a humoral immunological response that promotes opsonophagocytosis of cells infected with MTB microorganisms.

### Claim 11 (depends on 10)

The method of claim 10, wherein the chemical and/or physical treatment further comprises additional exposure to heat, alcohol, glutaraldehyde and/or sonication.

### Claim 12 (depends on 10)

The method of claim 10, wherein the MTB epitope is located on a peptidoglycan, a mycolic acid, a heat-shock protein, or a lipoarabinomannan glycolipid of MTB.

### Claim 13 (depends on 9)

The method of claim 9, wherein administration of the immunological composition clears MTB from the blood of the mammal.

### Claim 14 (depends on 9)

The method of claim 9, wherein the composition modulates immunity to drug-resistant MTB.

### Claim 15 (depends on 9)

The method of claim 9, wherein the composition is administered at a therapeutically-effective dose.

### Claim 16 (depends on 10)

The method of claim 10, wherein antibodies clear MTB from the blood of the mammal.

### Claim 17 (depends on 10)

The method of claim 10, wherein the antibodies modulate immunity to drug-resistant MTB.

### Claim 18 (depends on 10)

The method of claim 10, wherein the antibodies are administered at a therapeutically-effective dose.