# US 7,655,617 B2 · Conjugates of soluble peptidic compounds with membrane-binding agents

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

- Number: US 7,655,617 B2
- Document ID: US7655617B2
- Status: Granted
- Kind: B2
- Application number: 10/742,887
- Filed: 2003-12-23
- Published: 2004-12-30
- Granted: 2010-02-02
- Earliest claimed: 1996-07-15
- Assignees: AdProTech Limited
- Inventors: Richard Anthony Godwin Smith; Ian Dodd; Danuta Ewa Irena Mossakowkska
- Web page: https://patentgrep.com/patent/US7655617B2

## CPC

- C12N 9/6462: {u-Plasminogen activator (3.4.21.73), i.e. urokinase}
- A61K 47/54: the modifying agent being an organic compound
- 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)
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07C 323/41: Y being a hydrogen or an acyclic carbon atom
- C07C 323/59: with acylated amino groups bound to the carbon skeleton
- C07K 14/3153: {Streptokinase}
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C12Y 304/21073: u-Plasminogen activator (3.4.21.73), i.e. urokinase
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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)
- C12Y: ENZYMES

## Abstract

The present invention provides, among other things, soluble derivatives of soluble polypeptides that incorporate membrane binding elements. Methods of making these soluble derivatives, and methods of using these soluble derivatives also are provided.

## Claims

### Claim 1

A soluble compound that is directed to an outer membrane of a cell, wherein the soluble compound comprises:
(1) a therapeutic agent; and
(2) a membrane localization reagent, wherein the membrane localization reagent is soluble and comprises:
(a) at least one lipophilic binding element comprising aliphatic acyl groups;
(b) a hydrophilic peptide binding element comprising basic amino acids, wherein the hydrophilic binding element is bound to the lipophilic element; and
(c) a linker that covalently binds (i) the therapeutic agent to (ii) the hydrophilic peptide binding element of the membrane localization reagent to form the soluble compound.

### Claim 2 (depends on 1)

The soluble compound of claim 1, wherein the hydrophilic peptide binding element comprises lysine residues.

### Claim 3 (depends on 2)

The soluble compound of claim 2, wherein the hydrophilic peptide binding element comprises three to ten lysine residues.

### Claim 4 (depends on 3)

The soluble compound of claim 3, wherein the hydrophilic peptide binding element comprises four to seven lysine residues.

### Claim 5 (depends on 1)

The soluble compound of claim 1, wherein the hydrophilic peptide binding element comprises arginine residues.

### Claim 6 (depends on 5)

The soluble compound of claim 5, wherein the hydrophilic peptide binding element comprises three to ten arginine residues.

### Claim 7 (depends on 6)

The soluble compound of claim 6, wherein the hydrophilic peptide binding element comprises four to seven arginine residues.

### Claim 8 (depends on 1)

The soluble compound of claim 1, wherein the hydrophilic peptide binding element is selected from the group consisting of:
(a) DGPKKKKKKSPSKSSG;
(SEQ ID NO. 8)
(b) GSSKSPSKKKKKKPGD;
(SEQ ID NO. 9)
(c) SPSNETPKKKKKRFSFKKSG;
(SEQ ID NO. 10)
(d) DGPKKKKKKSPSKSSK;
(SEQ ID NO. 11)
and
(e) SKDGKKKKKKSKTK
(SEQ ID NO.12).

### Claim 9 (depends on 1)

The soluble compound of claim 1, wherein the hydrophilic peptide binding element comprises GSSKSPSKKKKKKPGD (SEQ ID NO. 9).

### Claim 10 (depends on 1)

The soluble compound of claim 1, wherein the lipophilic binding element comprises 8 to 18 methylene units.

### Claim 11 (depends on 10)

The soluble compound of claim 10, wherein the lipophilic binding element comprises 10 to 14 methylene units.

### Claim 12 (depends on 9)

The soluble compound of claim 9, wherein the lipophilic binding element comprises myristoyl.

### Claim 13 (depends on 11)

The soluble compound of claim 11, wherein the lipophilic binding element comprises myristoyl.

### Claim 14 (depends on 1)

The soluble compound according to claim 1, wherein the therapeutic agent comprises Short Consensus Repeats 1-3 of Long Homologous Repeat A of Complement Receptor 1.