# US 11,440,951 B2 · Therapeutic antibodies to Marburg virus

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

- Number: US 11,440,951 B2
- Document ID: US11440951B2
- Status: Granted
- Kind: B2
- Application number: 16/491,672
- Filed: 2018-03-09
- Published: 2020-12-31
- Granted: 2022-09-13
- Earliest claimed: 2017-03-13
- Assignees: The Government of the United States, as represented by the Secretary of the Army
- Applicants: The Government of the United States, as Represented by the Secretary of the Army; Philippe Thullier
- Inventors: Philippe Thullier; Jeffrey Froude, II; John Dye, Jr.
- Web page: https://patentgrep.com/patent/US11440951B2

## CPC

- C07K 16/10: RNA viruses
- A61K 39/42: viral
- A61P 31/14: for RNA viruses
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- 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 2317/622: Single chain antibody (scFv)
- C07K 2317/64: comprising a combination of variable region and constant region components
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/00: Fusion polypeptide
- 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

Provided here are immunoglobulins and compositions containing one or more of said immunoglobulins reactive to a strain of Marburg virus. The immunoglobulins and compositions comprising said immunoglobulins can be used prophylactically to prevent a Marburg virus infection or to treat a patient that has been exposed to a Marburg virus in order to reduce a symptom.

## Claims

### Claim 1

A composition comprising a reactive anti-Marburg immunoglobulin and a pharmaceutically acceptable carrier, wherein the immunoglobulin comprises VH complementarity determining regions (CDRs) of:
a VH CDR1 corresponding to amino acid residues of 26-33 of SEQ ID NO: 1;
a VH CDR2 corresponding to amino acid residues of 51-58 of SEQ ID NO: 1; and
a VH CDR3 corresponding to amino acid residues of 97-107 of SEQ ID NO: 1;
and VL CDRs of:
a VL CDR1 corresponding to amino acid residues of 27-32 of SEQ ID NO: 2;
a VL CDR2 corresponding to amino acid residues of 50-52 of SEQ ID NO: 2; and
a VL CDR3 corresponding to amino acid residues of 89-97 of SEQ ID NO: 2.

### Claim 2 (depends on 1)

The composition of claim 1, wherein said composition is reactive to a strain of Marburg virus.

### Claim 3 (depends on 2)

The composition of claim 2, wherein the Marburg virus strain is Ci67, Ravn, Musoke, or Angola.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the composition further comprises at least one other immunoglobulin selected from the group consisting of:
(a) immunoglobulin R4G7 having a variable heavy chain (VH) of SEQ ID NO: 9 and a variable light chain (VL) of SEQ ID NO: 10;
(b) immunoglobulin R4G10 having a VH of SEQ ID NO: 11 and a VL of SEQ ID NO: 12;
(c) immunoglobulin R4G11 having a VH of SEQ ID NO: 13 and a VL of SEQ ID NO: 14;
(d) immunoglobulin R3C4 having a VH of SEQ ID NO: 15 and a VL of SEQ ID NO: 16;
(e) immunoglobulin R4G8 having a VH of SEQ ID NO: 17 and a VL of SEQ ID NO: 18;
(f) immunoglobulin R3D4 having a VH of SEQ ID NO: 19 and a VL of SEQ ID NO: 20;
(g) immunoglobulin R3G2 having a VH of SEQ ID NO: 21 and a VL of SEQ ID NO: 22;
(h) immunoglobulin R3G5 having a VH of SEQ ID NO: 23 and a VL of SEQ ID NO: 24;
(i) immunoglobulin R4H12 having a VH of SEQ ID NO: 25 and a VL of SEQ ID NO: 26; and
(j) immunoglobulin R3H2 having a VH of SEQ ID NO: 27 and a VL of SEQ ID NO: 28.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the immunoglobulin has at least 90% sequence identity respectively to VH and VL sequences of SEQ ID NO: 1 and 2.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the strain of Marburg virus is selected from the group consisting of Ci67, Ravn, Musoke, and Angola.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the anti-Marburg virus immunoglobulin is R3F6 having a variable heavy chain of SEQ ID NO: 1 and a variable light chain of SEQ ID NO: 2.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the immunoglobulin is a bispecific antibody, a scFv, a Fab, or a diabody.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the immunoglobulin is a humanized antibody.

### Claim 10 (depends on 1)

A method of protecting a subject from exposure to a Marburg virus strain comprising administering to said subject an effective amount of the composition of claim 1 prior to exposure to said Marburg virus.

### Claim 11 (depends on 10)

The method of claim 10, wherein the composition comprises an immunoglobulin that is engineered for extended release, and wherein said the effective amount is an amount of about 5 to about 50 mg/kg of subject weight.

### Claim 12 (depends on 10)

The method of claim 10, wherein the subject is administered the composition more than once.

### Claim 13 (depends on 1)

A method of inhibiting progression of a Marburg virus infection in a subject after the subject is exposed to said Marburg virus comprising administering at least one effective amount of the composition of claim 1.

### Claim 14 (depends on 13)

The method of claim 13, wherein the effective amount of the composition is administered within one week after exposure to a Marburg virus, wherein the composition is administered intravenously or subcutaneously at a dosage of about 25 to about 150 mg/kg of subject weight.

### Claim 15 (depends on 1)

The composition of claim 1, wherein the immunoglobulin has at least 95% sequence identity respectively to VH and VL sequences of SEQ ID NO: 1 and 2.

### Claim 16 (depends on 1)

The composition of claim 1, wherein the immunoglobulin has at least 97% sequence identity respectively to VH and VL sequences of SEQ ID NO: 1 and 2.

### Claim 17 (depends on 1)

The composition of claim 1, wherein the immunoglobulin has at least 98% sequence identity respectively to VH and VL sequences of SEQ ID NO: 1 and 2.

### Claim 18 (depends on 1)

The composition of claim 1, wherein the immunoglobulin has at least 99% sequence identity respectively to VH and VL sequences of SEQ ID NO: 1 and 2.

### Claim 19

An immunoglobulin that is reactive to a strain of Marburg virus, wherein the immunoglobulin is selected from the group consisting of:
(a) an immunoglobulin comprising VH complementarity determining regions (CDRs) of:
a VH CDR1 corresponding to amino acid residues of 26-33 of SEQ ID NO: 1;
a VH CDR2 corresponding to amino acid residues of 51-58 of SEQ ID NO: 1; and
a VH CDR3 corresponding to amino acid residues of 97-107 of SEQ ID NO: 1;
and VL CDRs of:
a VL CDR1 corresponding to amino acid residues of 27-32 of SEQ ID NO: 2;
a VL CDR2 corresponding to amino acid residues of 50-52 of SEQ ID NO: 2; and
a VL CDR3 corresponding to amino acid residues of 89-97 of SEQ ID NO: 2;
(b) immunoglobulin R4G7 having a VH of SEQ ID NO: 9 and a VL of SEQ ID NO: 10;
(c) immunoglobulin R4G10 having a VH of SEQ ID NO: 11 and a VL of SEQ ID NO: 12;
(d) immunoglobulin R4G11 having a VH of SEQ ID NO: 13 and a VL of SEQ ID NO: 14;
(e) immunoglobulin R3C4 having a VH of SEQ ID NO: 15 and a VL of SEQ ID NO: 16;
(f) immunoglobulin R4G8 having a VH of SEQ ID NO: 17 and a VL of SEQ ID NO: 18;
(g) immunoglobulin R3D4 having a VH of SEQ ID NO: 19 and a VL of SEQ ID NO: 20;
(h) immunoglobulin R3G2 having a VH of SEQ ID NO: 21 and a VL of SEQ ID NO: 22;
(i) immunoglobulin R3G5 having a VH of SEQ ID NO: 23 and a VL of SEQ ID NO: 24;
(j) immunoglobulin R4H12 having a VH of SEQ ID NO: 25 and a VL of SEQ ID NO: 26; and
(k) immunoglobulin R3H2 having a VH of SEQ ID NO: 27 and a VL of SEQ ID NO: 28.
