# US 2019/0169282 A1 · Antigen Binding Proteins that Bind DLL-4

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- Number: US 2019/0169282 A1
- Document ID: US20190169282A1
- Status: Published application
- Kind: A1
- Application number: 16/241,828
- Filed: 2019-01-07
- Published: 2019-06-06
- Earliest claimed: 2012-05-31
- Assignees: Sorrento Therapeutics, Inc.
- Applicants: Sorrento Therapeutics, Inc.
- Inventors: Edwige GROS; Yanliang ZHANG; Heyue ZHOU; Randy GASTWIRT
- Web page: https://patentgrep.com/patent/US20190169282A1

## CPC

- C07K 16/22: against growth factors {; against growth regulators}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 2317/21: from primates, e.g. man
- 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: 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

There is disclosed compositions and methods relating to or derived from anti-DLL-4 antibodies. More specifically, there is disclosed fully human antibodies that bind DLL-4, DLL-4-binding fragments and derivatives of such antibodies, and DLL-4-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having DLL-4 related disorders or conditions, including various inflammatory disorders and various cancers.

## Claims

### Claim 1

A method for treating a broad spectrum of mammalian cancers, comprising administering an effective amount of an antibody that binds to a Delta-like 4 (DLL-4) epitope, the antibody comprising: a heavy chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 5, and SEQ ID NO. 7; and that has a light chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 2, SEQ ID NO. 6, and SEQ ID NO. 8.

### Claim 2 (depends on 1)

The method of claim 1, wherein the antibody has-comprises a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 1/SEQ ID NO. 2, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.

### Claim 3

A method for treating a broad spectrum of mammalian cancers, comprising administering an effective amount of an antibody Fab fragment that binds to a DLL-4, epitope, the Fab fragment comprising: a heavy chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 5, and SEQ ID NO. 7, and a light chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 2, SEQ ID NO. 6, and SEQ ID NO. 8.

### Claim 4 (depends on 3)

The method of claim 3, wherein the Fab fragment comprises a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 1/SEQ ID NO. 2, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.

### Claim 5

A method for treating a broad spectrum of mammalian cancers, comprising administering an effective amount of a single chain antibody, or fragment thereof, that binds to a DLL-4 epitope, the single chain antibody comprising: a heavy chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 5, and SEQ ID NO. 7, and a light chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 2, SEQ ID NO. 6, and SEQ ID NO. 8, wherein the heavy chain variable domain and the light chain variable domain are connected by a peptide linker.

### Claim 6 (depends on 5)

The method of claim 5, wherein the single chain antibody, or fragment thereof, comprises a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 1/SEQ ID NO. 2, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.

### Claim 7

A method for treating a broad spectrum of mammalian cancers, comprising administering an effective amount of an antibody that binds to a DLL-4 epitope, the antibody comprising:
(a) a heavy chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 1, 5, or 7; and
(b) a light chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 2, 6, or 8.

### Claim 8 (depends on 7)

The method of claim 7, wherein the antibody comprises:
(a) a heavy chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 1; and
(b) a light chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 2.

### Claim 9 (depends on 7)

The method of claim 7, wherein the antibody comprises:
(a) a heavy chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 5; and
(b) a light chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 6.

### Claim 10 (depends on 7)

The method of claim 7, wherein the antibody comprises:
(a) a heavy chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 7; and
(b) a light chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 8.

### Claim 11

A method for treating a broad spectrum of mammalian cancers, comprising administering an effective amount of an antibody that binds to a DLL-4 epitope, the antibody comprising a heavy chain variable domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO. 1, 5, and 7, and further comprising a light chain.

### Claim 12 (depends on 11)

The method of claim 11, wherein the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 1.

### Claim 13 (depends on 11)

The method of claim 11, wherein the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 5.

### Claim 14 (depends on 11)

The method of claim 11, wherein the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 7.

### Claim 15

A method for treating a broad spectrum of mammalian cancers, comprising administering an effective amount of an antibody that binds to a DLL-4 epitope, the antibody comprising a light chain variable domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO. 2, 6, and 8, and further comprising a heavy chain.

### Claim 16 (depends on 15)

The method of claim 15, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 2.

### Claim 17 (depends on 15)

The method of claim 15, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 6.

### Claim 18 (depends on 15)

The method of claim 15, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 8

### Claim 19

A method for treating a broad spectrum of mammalian cancers, comprising administering an effective amount of an antibody that binds to a DLL-4 epitope, wherein the antibody comprises a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 1/SEQ ID NO. 2, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.

### Claim 20 (depends on 19)

The method of claim 19, wherein the the heavy chain/light chain variable domain sequence is SEQ ID NO. 1/SEQ ID NO. 2.

### Claim 21 (depends on 19)

The method of claim 19, wherein the the heavy chain/light chain variable domain sequence is SEQ ID NO. 5/SEQ ID NO. 6.

### Claim 22 (depends on 19)

The method of claim 19, wherein the the heavy chain/light chain variable domain sequence is SEQ ID NO. 7/SEQ ID NO. 8.

### Claim 23 (depends on 1)

The method of claim 1, wherein the antibody is selected from the group consisting of a Fab, a Fab′, a F(ab′)2, an Fv, a domain antibody (dAb), a single-chain antibody, a chimeric antibody, a diabody, a triabody, a tetrabody, a fully human antibody, a humanized antibody, and a chimeric antibody.

### Claim 24 (depends on 23)

The method of claim 23, wherein the antibody is an IgG.

### Claim 25 (depends on 7)

The method of claim 7, wherein wherein the antibody is selected from the group consisting of a Fab, a Fab′, a F(ab′)2, an Fv, a domain antibody (dAb), a single-chain antibody, a chimeric antibody, a diabody, a triabody, a tetrabody, a fully human antibody, a humanized antibody, and a chimeric antibody.

### Claim 26 (depends on 25)

The method of claim 25, wherein the antibody is a Fab.

### Claim 27 (depends on 25)

The method of claim 25, wherein the antibody is a single chain antibody.

### Claim 28 (depends on 25)

The method of claim 25, wherein the antibody, wherein the antibody is an IgG.