# US 7,091,325 B2 · Fibrin/fibrinogen-binding conjugate

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- Number: US 7,091,325 B2
- Document ID: US7091325B2
- Status: Granted
- Kind: B2
- Application number: 10/749,832
- Filed: 2003-12-30
- Published: 2004-09-30
- Granted: 2006-08-15
- Earliest claimed: 2000-09-25
- Assignees: Baxter Aktiengesellschaft; Baxter International Inc.
- Inventors: Heinz Redl; Walter Fuerst; Rudolf Kneidinger; Sam L. Helgerson; Douglas Looker; Elisabeth M. Inman; Jane P. Richards; Catalina Wong
- Web page: https://patentgrep.com/patent/US7091325B2

## CPC

- C07K 14/745: Blood coagulation or fibrinolysis factors
- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- A61K 47/6435: {the peptide or protein in the drug conjugate being a connective tissue peptide, e.g. collagen, fibronectin or gelatin}
- A61K 47/665: {the pre-targeting system, clearing therapy or rescue therapy involving biotin-(strept) avidin systems}
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- 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: 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)
- 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
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES

## Abstract

A fibrin/fibrinogen binding conjugate for forming a depot for the sustained release of a pharmaceutically active substance from a fibrin clot. The conjugate comprises a fibrin/fibrinogen binding moiety bound to a pharmaceutically active substance either directly or via an intervening substance capturing moiety such as an antibody. The conjugate can also be a recombinant fusion protein comprising a fibrin/fibrinogen binding moiety such as VEGF165 C-terminal domain fused to a wound-healing substance such as leptin.

## Claims

### Claim 1

Fibrin/fibrinogen-binding conjugate comprising
a fibrin/fibrinogen-binding moiety that is a nucleic acid,
a substance capturing moiety capable of reversibly binding to a pharmaceutically active substance,
wherein said fibrin/fibrinogen-binding moiety is bound to said substance capturing moiety.

### Claim 2 (depends on 1)

The conjugate of claim 1, wherein said substance capturing moiety is an antibody, a receptor or a part thereof which specifically recognizes said pharmaceutically active substance.

### Claim 3 (depends on 1)

The conjugate of claim 1, further comprising a pharmaceutically active substance.

### Claim 4 (depends on 3)

The conjugate of claim 3, wherein said pharmaceutically active substance is selected from the group consisting of antibiotics, growth factors, receptors for tissue components, tissue adhesive substances, nucleic acids, plasma proteins, hormones, heparinoids, wound-healing substances, and imaging agents.

### Claim 5 (depends on 1)

The conjugate of claim 1, wherein said fibrin/fibrinogen-binding moiety and said substance capturing moiety are covalently bound.

### Claim 6

Fibrin/fibrinogen-binding conjugate comprising
a fibrin/fibrinogen-binding moiety selected from the group consisting of fibronectin, bacterial fibrinogen binding proteins, integrins, and moieties derived from any member of this group,
a substance capturing moiety that is an antibody or a part thereof which specifically recognizes a pharmaceutically active substance, and
the pharmaceutically active substance,
wherein said fibrin/fibrinogen-binding moiety is bound to said substance capturing moiety.

### Claim 7

Fibrin/fibrinogen-binding conjugate comprising
a fibrin/fibrinogen-binding moiety selected from the group consisting of fibronectin, bacterial fibrinogen binding proteins, integrins, and moieties derived from any member of this group,
a substance capturing moiety that is an antibody or a part thereof which specifically recognizes a pharmaceutically active substance,
wherein said fibrin/fibrinogen-binding moiety is bound to said substance capturing moiety.

### Claim 8 (depends on 6)

The conjugate of claim 6, wherein said pharmaceutically active substance is selected from the group consisting of antibiotics, growth factors, receptors for tissue components, tissue adhesive substances, nucleic acids, plasma proteins, hormones, heparinoids, and imaging agents.

### Claim 9 (depends on 6)

The conjugate of claim 6, wherein said fibrin/fibrinogen-binding moiety and said substance capturing moiety are covalently bound.

### Claim 10 (depends on 6)

The conjugate of claim 6, wherein said pharmaceutically active substance is a wound healing substance.

### Claim 11 (depends on 7)

The conjugate of claim 7, wherein said fibrin/fibrinogen-binding moiety and said substance capturing moiety are covalently bound.

### Claim 12 (depends on 7)

The conjugate of claim 7 wherein said pharmaceutically active substance is selected from the group consisting of antibiotics, growth factors, receptors for tissue components, tissue adhesive substances, nucleic acids, plasma proteins, hormones, heparinoids, and imaging agents.

### Claim 13 (depends on 7)

The conjugate of claim 7, wherein said pharmaceutically active substance is a wound healing substance.
