# US 2016/0193298 A1 · Therapeutic use of vegf-c and ccbe1

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

- Number: US 2016/0193298 A1
- Document ID: US20160193298A1
- Status: Published application
- Kind: A1
- Application number: 14/911,920
- Filed: 2014-08-13
- Published: 2016-07-07
- Earliest claimed: 2013-08-14
- Assignees: Laurantis Pharma Oy
- Applicants: Laurantis Pharma Oy
- Inventors: Kari ALITALO; Michael JELTSCH; Andrey ANISIMOV
- Web page: https://patentgrep.com/patent/US20160193298A1

## CPC

- A61K 38/1866: {Vascular endothelial growth factor [VEGF]}
- A61K 38/1709: {from mammals}
- A61K 38/1738: {Calcium binding proteins, e.g. calmodulin}
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61P 7/10: Antioedematous agents; Diuretics
- C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- C07K 2319/036: targeting to the medium outside of the cell, e.g. type III secretion
- C12N 15/85: for animal cells
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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 present invention relates to therapeutic methods, uses and compositions comprising CCBE1 and VEGF-C for treating disorders and conditions involving impaired lymphatic system, particularly lymphedema.

## Claims

### Claim 1

A composition comprising:
I) a first component comprising at least one of the group consisting of:
a) full-length CCBE1,
b) a fragment of CCBE1 having the ability to cleave full-length VEGF-C,
c) an amino acid sequence having at least 80% identity to full-length CCBE1 or to said fragment of CCBE1, wherein said amino acid sequence has the ability to cleave full-length VEGF-C, and
d) a polynucleotide encoding any of a) through c) above; and
II) a second component comprising at least one of the group consisting of:
e) VEGF-C,
f) a fragment of VEGF-C having the ability to bind to, and activate VEGFR-2 and/or VEGFR-3,
g) an amino acid sequence having at least 80% identity to full-length VEGF-C or to said fragment of VEGF-C, wherein said amino acid sequence has the ability to bind to, and activate, VEGFR-2 and/or VEGFR-3, and
h) a polynucleotide encoding any of e) through g) above.

### Claim 2 (depends on 1)

The composition according to claim 1, wherein the CCBE1 is in the form of a polypeptide comprising amino acids 35-406 set forth in SEQ ID NO: 1, or an amino acid sequence having at least 80% amino acid sequence identity therewith.

### Claim 3 (depends on 1)

The composition according to claim 1, comprising a polynucleotide comprising a nucleic acid sequence set forth in SEQ ID NO: 2 or a nucleic acid sequence having at least 80% nucleic acid sequence identity therewith.

### Claim 4 (depends on 1)

The composition according to claim 1, wherein the VEGF-C is in the form of a polypeptide comprising an amino acid sequence selected from the group consisting of amino acids 32-419 of SEQ ID NO: 3; amino acids 32-227 covalently linked to amino acids 228-419 of SEQ ID NO: 3; amino acids 112-227 of SEQ ID NO: 3; and amino acids 103-227 of SEQ ID NO: 3; and an amino acid sequence having at least 80% amino acid sequence identity therewith.

### Claim 5 (depends on 1)

The composition according to claim 1, comprising a polynucleotide comprising a nucleic acid sequence selected from the group consisting of nucleic acids 524-1687 of SEQ ID NO: 4; nucleic acids 737-1687 of SEQ ID NO: 4; nucleic acids 764-1687 of SEQ ID NO: 4; nucleic acids 737-1111 of SEQ ID NO: 4; nucleic acids 764-1111 of SEQ ID NO: 4 and a nucleic acid sequence having at least 80% nucleic acid sequence identity therewith.

### Claim 6

(canceled)

### Claim 7 (depends on 1)

The composition, according to claim 1, further comprising a pharmaceutically acceptable vehicle.

### Claim 8

A method of treating lymphedema by administering to a patient in need thereof:
I) a first component comprising at least one of the group consisting of:
a) full-length CCBE1,
b) a fragment of CCBE1 having the ability to cleave full-length VEGF-C,
c) an amino acid sequence having at least 80% identity to full-length CCBE1 or to said fragment of CCBE1, wherein said amino acid sequence has the ability to cleave full-length VEGF-C, and
d) a polynucleotide encoding any of a) through c) above; and
II) a second component comprising at least one of the group consisting of:
e) V EGF-C,
f) a fragment of VEGF-C having the ability to bind to and activate VEGFR-2 and/or VEGFR-3,
g) an amino acid sequence having at least 80% identity to full-length VEGF-C or to said fragment of VEGF-C, wherein said amino acid sequence has the ability to bind to and activate, VEGFR-2 and/or VEGFR-3, and
h) a polynucleotide encoding any of e) through g) above;
wherein said first and second compounds are administered simultaneously, separately or sequentially.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the CCBE1 is administered in the form of a polypeptide comprising amino acids 35-406 set forth in SEQ ID NO: 1, or an amino acid sequence having at least 80% amino acid sequence identity therewith.

### Claim 10 (depends on 8)

The method according to claim 8, wherein the CCBE1 is administered via a polynucleotide comprising a nucleic acid sequence set forth in SEQ ID NO: 2 or a nucleic acid sequence having at least 80% nucleic acid sequence identity therewith.

### Claim 11 (depends on 8)

The method according to claim 8, wherein the VEGF-C is administered in the form of a polypeptide comprising an amino acid sequence selected from the group consisting of amino acids 32-419 of SEQ ID NO: 3; amino acids 32-227 covalently linked to amino acids 228-419 of SEQ ID NO: 3; amino acids 112-227 of SEQ ID NO: 3; amino acids 103-227 of SEQ ID NO: 3; and an amino acid sequence having at least 80% amino acid sequence identity therewith.

### Claim 12 (depends on 8)

The method according to claim 8, wherein the VEGF-C is administered in the form of a polynucleotide comprising a nucleic acid sequence selected from the group consisting of nucleic acids 524-1687 of SEQ ID NO: 4; nucleic acids 737-1687 of SEQ ID NO: 4; nucleic acids 764-1687 of SEQ ID NO: 4; nucleic acids 737-1111 of SEQ ID NO: 4; nucleic acids 764-1111 of SEQ ID NO: 4; and a nucleic acid sequence having at least 80% nucleic acid sequence identity therewith.

### Claim 13 (depends on 8)

The method according to claim 8, wherein the lymphedema is selected from the group consisting of primary lymphedema, Milroy's syndrome, Meige's lymphedema, lymphedema tarda, secondary lymphedema, and lipedema.