# US 10,307,478 B2 · Biochemically stabilized HIV-1 Env trimer vaccine

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- Number: US 10,307,478 B2
- Document ID: US10307478B2
- Status: Granted
- Kind: B2
- Application number: 15/919,834
- Filed: 2018-03-13
- Published: 2018-07-26
- Granted: 2019-06-04
- Earliest claimed: 2008-10-10
- Assignees: Beth Israel Deaconess Medical Center, Inc.; Children's Medical Center Corporation
- Applicants: Beth Israel Deaconess Medical Center; Children's Medical Center Corporation
- Inventors: Stephen C. Harrison; Bing Chen; Dan H. Barouch; Joseph P. Nkolola; Michael Scott Seaman
- Web page: https://patentgrep.com/patent/US10307478B2

## CPC

- A61K 39/21: Retroviridae, e.g. equine infectious anemia virus
- A61K 39/12: Viral antigens
- A61P 31/18: for HIV
- A61P 37/04: Immunostimulants
- C07K 14/005: from viruses
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/54: {characterised by the route of administration}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59}
- A61K 2039/575: {humoral response}
- C12N 2740/16051: Methods of production or purification of viral material
- C12N 2740/16122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2740/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2740/16171: Demonstrated in vivo effect
- 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)

## Abstract

Stabilized trimers of a clade A strain and a clade C strain of HIV-1 are provided. Broadly neutralizing antisera against HIV-1, methods of making broadly neutralizing antisera against HIV-1, broadly neutralizing vaccines against HIV-1, as well as methods of treating subjects infected with HIV, preventing HIV infection, and inhibiting HIV-mediated activities are also provided.

## Claims

### Claim 1

An immunogenic composition comprising:
an isolated gp140 polypeptide trimer, wherein the trimer comprises three identical polypeptide sequences, each polypeptide sequence comprising a gp140 polypeptide sequence that is at least 98% identical to residues 30-708 of SEQ ID NO:2.

### Claim 2 (depends on 1)

The immunogenic composition of claim 1, wherein the immunogenic composition elicits production of antibodies against HIV-1 after injection into a subject.

### Claim 3 (depends on 2)

The immunogenic composition of claim 2, wherein the antibodies comprise anti-HIV-1 clade C antibodies.

### Claim 4 (depends on 1)

The immunogenic composition of claim 1, wherein the gp140 polypeptide sequence includes an oligomerization domain.

### Claim 5 (depends on 4)

The immunogenic composition of claim 4, wherein the oligomerization domain is a T4 fibritin trimerization domain.

### Claim 6 (depends on 1)

The immunogenic composition of claim 1, wherein the gp140 polypeptide sequence that is at least 98% identical to residues 30-708 of SEQ ID NO:2 includes SEQ ID NO:8.

### Claim 7 (depends on 1)

The immunogenic composition of claim 1, wherein the gp140 polypeptide sequence that is at least 98% identical to residues 30-708 of SEQ ID NO:2 includes SEQ ID NO:6.

### Claim 8 (depends on 1)

The immunogenic composition of claim 1, wherein the gp140 polypeptide sequence that is at least 98% identical to residues 30-708 of SEQ ID NO:2 includes SEQ ID NO:8 and SEQ ID NO:6.

### Claim 9 (depends on 1)

The immunogenic composition of claim 1, wherein the polypeptide sequence comprising a gp140 polypeptide sequence is at least 99% identical to residues 30-708 of SEQ ID NO:2.

### Claim 10 (depends on 1)

The immunogenic composition of claim 1, further comprising an adjuvant.

### Claim 11

An isolated gp140 polypeptide trimer, wherein the gp140 polypeptide trimer comprises three identical gp140 polypeptides comprising an amino acid sequence at least 98% identical to residues 30-708 of SEQ ID NO:2.

### Claim 12 (depends on 11)

The gp140 polypeptide trimer of claim 11, wherein the gp140 polypeptide trimer elicits production of antibodies against HIV-1 after injection into a subject.

### Claim 13 (depends on 12)

The gp140 polypeptide trimer of claim 12, wherein the antibodies comprise anti-HIV -1 clade C antibodies.

### Claim 14 (depends on 11)

The gp140 polypeptide trimer of claim 11, wherein the gp140 polypeptide sequence includes an oligomerization domain.

### Claim 15 (depends on 14)

The gp140 polypeptide trimer of claim 14, wherein the oligomerization domain is a T4 fibritin trimerization domain.

### Claim 16 (depends on 11)

The gp140 polypeptide trimer of claim 11, wherein the gp140 polypeptide sequence that is at least 98% identical to residues 30-708 of SEQ ID NO:2 includes SEQ ID NO:8.

### Claim 17 (depends on 11)

The gp140 polypeptide trimer of claim 11, wherein the gp140 polypeptide sequence that is at least 98% identical to residues 30-708 of SEQ ID NO:2 includes SEQ ID NO:6.

### Claim 18 (depends on 11)

The gp140 polypeptide trimer of claim 11, wherein the gp140 polypeptide sequence that is at least 98% identical to residues 30-708 of SEQ ID NO:2 includes SEQ ID NO:8 and SEQ ID NO:6.

### Claim 19 (depends on 1)

A method of treating or inhibiting an HIV-1-mediated activity in a subject infected with HIV-1 comprising:
a. contacting a subject infected with HIV-1 with the immunogenic composition of claim 1; and
b. producing anti-HIV-1 antibodies in the subject to treat or inhibit the HIV-1 mediated activity in the subject infected with HIV-1.

### Claim 20 (depends on 19)

The method of claim 19, wherein the anti-HIV-1 antibodies are selected from one or more of anti-HIV-1 clade A antibodies, anti-HIV-1 clade B antibodies, and anti-HIV-1 clade C antibodies.

### Claim 21 (depends on 19)

The method of claim 19, wherein the HIV-1 titer in the subject infected with HIV-1is decreased after contacting the subject with the immunogenic composition.

### Claim 22 (depends on 19)

The method of claim 19, wherein the HIV-1 mediated activity is viral spread.

### Claim 23 (depends on 1)

A method of inducing an immune response against HIV-1 in a subject, the method comprising:
a. contacting a subject with the immunogenic composition of claim 1; and
b. inducing an immune response against HIV-1 in the subject.

### Claim 24 (depends on 23)

The method of claim 23, wherein the subject is not infected with HIV-1 at the moment of administration of the immunogenic composition.