# US 11,028,159 B2 · Composition and methods for treating snake envenomation

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- Number: US 11,028,159 B2
- Document ID: US11028159B2
- Status: Granted
- Kind: B2
- Application number: 16/610,836
- Filed: 2018-04-26
- Published: 2020-05-21
- Granted: 2021-06-08
- Earliest claimed: 2017-05-02
- Assignees: Venomyx, Inc.
- Applicants: Venomyx, Inc.
- Inventors: Daniel Thomas Dempsey; Deepankar Roy; Alexio Capovilla
- Web page: https://patentgrep.com/patent/US11028159B2

## CPC

- A61P 39/02: Antidotes
- C07K 16/18: against material from animals or humans
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- 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)

## Abstract

The invention generally relates to compositions and methods for treating snake envenomation in animals, including humans. In some aspects, the invention provides therapeutic compositions that contain one or more toxin binding molecules including, for example, anti-toxin antibodies and binding fragments.

## Claims

### Claim 1

A single-domain antibody (sdAb) that binds to snake venom metalloproteinase (SVMP), comprising an amino acid sequence which is at least 70% identical to SEQ ID NOs. 1 or 2.

### Claim 2

A single-domain antibody (sdAb) that binds to snake venom metalloproteinase (SVMP), wherein the sdAb comprises at least one single-variable region that includes a plurality of complementarity-determining regions (CDRs) including:
a CDR1 that exhibits 100% sequence identity to SEQ ID NOs. 6 or 7;
a CDR2 that exhibits 100% sequence identity to SEQ ID NOs. 11 or 12; and
a CDR3 that exhibits 100% sequence identity to SEQ ID NOs. 16 or 17.

### Claim 3 (depends on 2)

The sdAb of claim 2, wherein the at least one single-variable region further includes a plurality of framework regions (FRs) and has a general formula:
FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, wherein:
the FR1 exhibits 100% sequence identity to SEQ ID NOs. 21-22 or 26;
the FR2 exhibits 100% sequence identity to SEQ ID NOs. 27-28 or 32;
the FR3 exhibits 100% sequence identity to SEQ ID NOs. 33-34 or 38; and
the FR4 exhibits 100% sequence identity to SEQ ID NOs. 39 or 41.

### Claim 4 (depends on 2)

The sdAb of claim 2, wherein said sdAb is CDR-grafted, humanized, de-immunized, or selected by phage display.

### Claim 5

A single-domain antibody (sdAb) that binds to snake bungarotoxin, comprising an amino acid sequence identical to SEQ ID NO. 3.

### Claim 6

A single-domain antibody (sdAb) that binds to snake bungarotoxin, wherein the sdAb comprises at least one single-variable region that includes a plurality of complementarity-determining regions (CDRs) including:
a CDR1 identical to SEQ ID NO. 8;
a CDR2 identical to SEQ ID NO. 13; and
a CDR3 identical to SEQ ID NO. 18.

### Claim 7 (depends on 6)

The sdAb of claim 6, wherein the at least one single-variable region further includes a plurality of framework regions (FRs) and has a general formula:
FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, wherein
the FR1 exhibits 100% sequence identity to SEQ ID NOs. 23 or 26;
the FR2 exhibits 100% sequence identity to SEQ ID NOs. 29 or 32;
the FR3 exhibits 100% sequence identity to SEQ ID NOs. 35 or 38; and
the FR4 exhibits 100% sequence identity to SEQ ID NOs. 40 or 41.

### Claim 8 (depends on 6)

The sdAb of claim 6, wherein said sdAb is CDR-grafted, humanized, de-immunized, or selected by phage display.

### Claim 9

A single-domain antibody (sdAb) that binds to snake cobrotoxin, comprising an amino acid sequence identical to SEQ ID NO. 4.

### Claim 10

A single-domain antibody (sdAb) that binds to snake cobrotoxin, wherein the sdAb comprises at least one single-variable region that includes a plurality of complementarity-determining regions (CDRs) including:
a CDR1 identical to SEQ ID NO. 9;
a CDR2 identical to SEQ ID NO. 14; and
a CDR3 identical to SEQ ID NO. 19.

### Claim 11 (depends on 10)

The sdAb of claim 10, wherein the at least one single-variable region further includes a plurality of framework regions (FRs) and has a general formula:
FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, wherein:
the FR1 exhibits 100% sequence identity to SEQ ID NOs. 24 or 26;
the FR2 exhibits 100% sequence identity to SEQ ID NOs. 30 or 32;
the FR3 exhibits 100% sequence identity to SEQ ID NOs. 36 or 38; and
the FR4 exhibits 100% sequence identity to SEQ ID NOs. 39 or 41.

### Claim 12 (depends on 10)

The sdAb of claim 10, wherein said sdAb is CDR-grafted, humanized, de-immunized, or selected by phage display.

### Claim 13

A single-domain antibody (sdAb) that binds to snake venom phospholipase A2 (svPLA2), comprising an amino acid sequence identical to SEQ ID NO. 5.

### Claim 14

A single-domain antibody (sdAb) that binds to snake venom phospholipase A2 (svPLA2), wherein the sdAb comprises at least one single-variable region that includes a plurality of complementarity-determining regions (CDRs) including:
a CDR1 identical to SEQ ID NO. 10;
a CDR2 identical to SEQ ID NO. 15; and
a CDR3 identical to SEQ ID NO. 20.

### Claim 15 (depends on 14)

The sdAb of claim 14, wherein the at least one single-variable region further includes a plurality of framework regions (FRs) and has a general formula:
FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, wherein:
the FR1 exhibits 100% sequence identity to SEQ ID NOs. 25 or 26;
the FR2 exhibits 100% sequence identity to SEQ ID NOs. 31 or 32;
the FR3 exhibits 100% sequence identity to SEQ ID NOs. 37 or 38; and
the FR4 exhibits 100% sequence identity to SEQ ID NOs. 40 or 41.

### Claim 16 (depends on 14)

The sdAb of claim 14, wherein said sdAb is CDR-grafted, humanized, de-immunized, or selected by phage display.
