# US 2014/0194597 A1 · Modified chimeric polypeptides with improved pharmacokinetic properties

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- Number: US 2014/0194597 A1
- Document ID: US20140194597A1
- Status: Published application
- Kind: A1
- Application number: 14/109,999
- Filed: 2013-12-18
- Published: 2014-07-10
- Earliest claimed: 1999-06-08
- Assignees: Regeneron Pharmaceuticals, Inc.
- Applicants: Regeneron Pharmaceuticals, Inc.
- Inventors: Nicholas J. Papadopoulos; Samuel Davis; George D. Yancopoulos
- Web page: https://patentgrep.com/patent/US20140194597A1

## CPC

- C07K 14/71: for growth factors; for growth regulators
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/22: against growth factors {; against growth regulators}
- C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes}
- C12N 15/09: Recombinant DNA-technology
- C12N 15/10: Processes for the isolation, preparation or purification of DNA or RNA (chemical preparation of DNA or RNA C07H21/00; preparation of non-structural polynucleotides from microorganisms or with enzymes C12P19/34)
- 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)
- C07H 21/04: with deoxyribosyl as saccharide radical
- C07K 2319/00: Fusion polypeptide
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)

## Abstract

The present invention provides VEGF antagonists with improved pharmacokinetic properties. According to certain embodiments, a fusion polypeptide capable of antagonizing VEGF activity is provided comprising a modified extracellular ligand binding domain of a VEGF receptor fused to a multimerizing component.

## Claims

### Claim at position 1

1-14. (canceled)

### Claim 15

A chimeric polypeptide capable of antagonizing VEGF activity consisting of a modified extracellular ligand binding domain of a VEGF receptor fused to a multimerizing component,
wherein the modified extracellular ligand binding domain consists of an immunoglobulin-like (Ig) domain of human Flt1 and an Ig domain of human Flk1, wherein the Ig domain of human Flt1 is Ig domain 2, and wherein the Ig domain of human Flk1 is Ig domain 3,
wherein the chimeric polypeptide exhibits improved pharmacokinetic properties as compared to a chimeric polypeptide consisting of only Ig domains of Flt1.

### Claim 16 (depends on 15)

The chimeric polypeptide of claim 15, wherein the Ig domain 2 of Flt1 is located upstream of the Ig domain 3 of Flk1.

### Claim 17 (depends on 15)

The chimeric polypeptide of claim 15, wherein the Ig domain 2 of Flt1 is located downstream of the Ig domain 3 of Flk1.

### Claim 18 (depends on 15)

The chimeric polypeptide of claim 15, wherein the multimerizing component comprises an immunoglobulin domain.

### Claim 19 (depends on 18)

The chimeric polypeptide of claim 18, wherein the immunoglobulin domain is selected from the group consisting of the Fc domain of IgG, and the heavy chain of IgG.

### Claim 20

A chimeric polypeptide capable of antagonizing VEGF activity consisting of a modified extracellular ligand binding domain of a VEGF receptor fused to a multimerizing component,
wherein the modified extracellular ligand binding domain consists of one or two immunoglobulin-like (Ig) domains of human Flt1 and one or two Ig domains of human Flk1, wherein at least one of the Ig domains of human Flt1 is Ig domain 2, and wherein at least one of the Ig domains of human Flk1 is Ig domain 3, wherein the chimeric polypeptide exhibits improved pharmacokinetic properties as compared to a chimeric polypeptide consisting of only Ig domains of Flt1.

### Claim 21 (depends on 20)

The chimeric polypeptide of claim 20, wherein the Ig domain 2 of Flt1 is located upstream of the Ig domain 3 of Flk1.

### Claim 22 (depends on 20)

The chimeric polypeptide of claim 20, wherein the Ig domain 2 of Flt1 is located downstream of the Ig domain 3 of Flk1.

### Claim 23 (depends on 20)

The chimeric polypeptide of claim 20, wherein the multimerizing component comprises an immunoglobulin domain.

### Claim 24 (depends on 23)

The chimeric polypeptide of claim 23, wherein the immunoglobulin domain is selected from the group consisting of the Fc domain of IgG, and the heavy chain of IgG.

### Claim 25 (depends on 16)

The chimeric polypeptide of claim 16, wherein the chimeric polypeptide comprises SEQ ID NO:12.

### Claim 26 (depends on 16)

The chimeric polypeptide of claim 16, wherein the chimeric polypeptide comprises SEQ ID NO:16.