# US 11,299,531 B2 · Fusion protein comprising a ligand binding domain of VEGF and PDGF

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- Number: US 11,299,531 B2
- Document ID: US11299531B2
- Status: Granted
- Kind: B2
- Application number: 15/542,692
- Filed: 2016-03-10
- Published: 2017-12-28
- Granted: 2022-04-12
- Earliest claimed: 2015-03-11
- Assignees: Allgenesis Biotherapeutics Inc.; AP Biosciences, Inc.
- Applicants: Allgenesis Biotherapeutics Inc.; AP Biosciences, Inc.
- Inventors: Kevin Zen; Pei-Tzu Wu; Jeng-Horng Her; Huang-Tsu Chen; Jiun-Shyang Leou; Ching-Hsuan Hsu
- Web page: https://patentgrep.com/patent/US11299531B2

## CPC

- C07K 14/71: for growth factors; for growth regulators
- A61P 7/10: Antioedematous agents; Diuretics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 27/02: Ophthalmic agents
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/70: containing domain for protein-protein interaction
- 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
- 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)

## Abstract

Fusion proteins containing a PDGF binding portion, a VEGF binding portion, and an Fc antibody region are described. Also described are nucleic acids encoding the fusion proteins, compositions comprising the fusion proteins, and methods of using the fusion proteins for treating or preventing clinical conditions characterized by abnormal angiogenesis, such as vascular permeability, edema or inflammation.

## Claims

### Claim 1

A fusion protein consisting of:
a. a first peptide consisting of an Ig-like domain D2 of a VEGFR1 and an Ig-like domain D3 of a VEGFR2,
b. an Fc region of an antibody consisting of a CH2 and a CH3 region of IgG1,
c. a second peptide consisting of Ig-like domains D1 to D3 of a PDGFRβ, and
d. a linker peptide;
wherein the fusion protein is arranged from N-terminus to C-terminus in an order selected from (a)-(b)-(d)-(c) or (c)-(b)-(d)-(a);
and
wherein the fusion protein is capable of binding to a VEGF and a PDGF and inhibiting the activity of the VEGF and the activity of the PDGF.

### Claim 2 (depends on 1)

The fusion protein of claim 1, wherein:
a. the Ig-like domain D2 of the VEGFR1 and the Ig-like domain D3 of the VEGFR2 consists of an amino acid sequence having at least 90% identity to SEQ ID NO: 7;
b. the Fc region of the antibody consists of an amino acid sequence having at least 90% identity to SEQ ID NO: 12; and
c. the Ig-like domains D1 to D3 of the PDGFRβ consists of an amino acid sequence having at least 90% identity to SEQ ID NO: 2.

### Claim 3 (depends on 2)

The fusion protein of claim 2, wherein:
a. the Ig-like domain D2 of the VEGFR1 and the Ig-like domain D3 of the VEGFR2 consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 7 and 10;
b. the Fc region of the antibody consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 12 and 15; and
c. the Ig-like domains D1 to D3 of the PDGFRβ consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 2 and 5.

### Claim 4 (depends on 1)

The fusion protein of claim 1, wherein the linker peptide consists of the amino acid sequence of SEQ ID NO: 20 or 24.

### Claim 5

A fusion protein consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 38, SEQ ID NO: 40, amino acids 20-766 of SEQ ID NO: 42, amino acids 21-769 of SEQ ID NO: 44 and amino acids 20-768 of SEQ ID NO: 50.

### Claim 6 (depends on 5)

The fusion protein of claim 5, consisting of an amino acid sequence selected from amino acids 21-769 of SEQ ID NO: 44 or amino acids 20-768 of SEQ ID NO: 50.

### Claim 7 (depends on 1)

An isolated nucleic acid molecule encoding the fusion protein of claim 1.

### Claim 8 (depends on 1)

A host cell comprising a nucleic acid molecule encoding the fusion protein of claim 1.

### Claim 9 (depends on 1)

A method of producing the fusion protein of claim 1, comprising:
a. culturing a host cell comprising a nucleic acid molecule encoding the fusion protein of claim 1, under a condition that the fusion protein is produced; and
b. recovering the fusion protein produced by the host cell.

### Claim 10 (depends on 1)

A pharmaceutical composition comprising the fusion protein of claim 1 and a pharmaceutically acceptable carrier.

### Claim 11 (depends on 1)

A method of inhibiting the activity of at least one of a VEGFR and a PDGFR in a subject in need thereof, comprising administering to a subject in need thereof an effective amount of the fusion protein of claim 1.

### Claim 12 (depends on 11)

The method of claim 11, wherein the subject is in need of a treatment of an ocular neovascular disorder selected from the group consisting of choroidal neovascularization (CNV), wet age-related macular degeneration, geographic atrophy, and diabetic retinopathy.

### Claim 13 (depends on 6)

A pharmaceutical composition comprising the fusion protein of claim 6, wherein the fusion protein consists of amino acids 21-769 of SEQ ID NO: 44.

### Claim 14 (depends on 13)

A method of inhibiting the activity of at least one of a VEGFR and a PDGFR in a subject in need thereof, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 13.

### Claim 15 (depends on 14)

The method of claim 14, wherein the subject is in need of a treatment of an ocular neovascular disorder selected from the group consisting of choroidal neovascularization (CNV), wet age-related macular degeneration, geographic atrophy, and diabetic retinopathy.

### Claim 16 (depends on 6)

A pharmaceutical composition comprising the fusion protein of claim 6, wherein the fusion protein consists of amino acids 20-768 of SEQ ID NO: 50.

### Claim 17 (depends on 16)

A method of inhibiting the activity of at least one of a VEGFR and a PDGFR in a subject in need thereof, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 16.

### Claim 18 (depends on 17)

The method of claim 17, wherein the subject is in need of a treatment of an ocular neovascular disorder selected from the group consisting of choroidal neovascularization (CNV), wet age-related macular degeneration, geographic atrophy, and diabetic retinopathy.