# US 5,700,444 A · Chemotactic peptide pharmaceutical applications

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- Number: US 5,700,444 A
- Document ID: US5700444A
- Status: Granted
- Kind: A
- Application number: 08/087,219
- Filed: 1993-07-02
- Granted: 1997-12-23
- Earliest claimed: 1992-02-20
- Assignees: Rhomed Incorporated
- Inventors: Paul O. Zamora; Richard J. Freer
- Web page: https://patentgrep.com/patent/US5700444A

## CPC

- C07K 7/06: having 5 to 11 amino acids
- A61K 49/14: Peptides, e.g. proteins
- A61K 51/08: Peptides, e.g. proteins {, carriers being peptides, polyamino acids, proteins}
- C07K 5/081: {the side chain containing O or S as heteroatoms, e.g. Cys, Ser}
- C07K 14/001: {by chemical synthesis}
- C07K 14/52: Cytokines; Lymphokines; Interferons
- C07K 14/655: Somatostatins
- C07K 14/78: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
- 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)
- A61K 2121/00: Preparations for use in therapy
- A61K 2123/00: Preparations for testing in vivo
- 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)

## Abstract

High affinity chemotactic peptides containing a biological-function domain which includes at least two linked N-formyl-Met-Leu-Phe sequences and a medically useful metal ion-binding domain are labeled with medically useful metal ions for use in a variety of diseases and pathologic conditions, and particularly for diagnosis and treatment of infections, inflammations and other diseases and conditions.

## Claims

### Claim 1

A high affinity chemotactic peptide-based pharmaceutical composition suitable for administration to a patient comprising:
a biological-function domain including at least two linked N-formyl-Met-Leu-Phe sequences wherein the sequences are linked by means of peptide side chains; and
a medically useful metal ion-binding domain comprising a sequence of amino acids containing sulfur or nitrogen atoms which are available for metal ion binding.

### Claim 2 (depends on 1)

The peptide-based pharmaceutical composition of claim 1 wherein said peptide comprising a biological-function domain and a medically useful metal ion-binding domain is selected from the group consisting of
(R.sub.1)--›Y.sub.1 !.sub.n --(R.sub.2),
(R.sub.1)--›Y.sub.1 --(R.sub.2)--Y.sub.1 !.sub.n --(R.sub.3)
and (R.sub.1)--›Y.sub.1 --(R.sub.2)--Y.sub.2 !.sub.n --(R.sub.3)
wherein,
the medically useful metal ion-binding domain is selected from one of the group consisting of ›Y.sub.1 !.sub.n, ›Y.sub.1 --(R.sub.2)--Y.sub.1 !.sub.n and ›Y.sub.1 --(R.sub.2)--Y.sub.2 !.sub.n in which n is a number between 1 and about 6 and Y.sub.1 and Y.sub.2 are amino acids comprising a sulfur, nitrogen or oxygen which is available for binding to metal ions or can be made available for binding to metal ions;
the biological-function domain comprises at least one of the group consisting of R.sub.1, R.sub.2 and R.sub.3 ; and
those portions of R.sub.1, R.sub.2 and R.sub.3 not comprising the biological-function domain each comprise an amino acid sequence containing from 0 to about 20 amino acids.

### Claim 3 (depends on 2)

The peptide-based pharmaceutical composition of claim 2 wherein the medically useful metal ion-binding domain comprises at least one amino acid sequence consisting of at least one amino acid selected from the group consisting of cysteine, cystine, histidine, penicillamine, deacylated methionine, lysine, arginine, aspartic acid, glutamic acid and tyrosine.

### Claim 4 (depends on 1)

The peptide-based pharmaceutical composition of claim 1 wherein said biological-function domain is a peptide sequence and linking agent comprising ##STR13##

### Claim 5 (depends on 1)

The peptide-based pharmaceutical composition of claim 1 wherein said composition further comprises a metal ion labeling agent.

### Claim 6 (depends on 5)

The peptide-based pharmaceutical composition of claim 5 wherein said metal ion labeling agent comprises a stannous ion agent.

### Claim 7 (depends on 5)

The peptide-based pharmaceutical composition of claim 5 wherein said stannous ion agent comprises a member selected from the group consisting of stannous tartrate, stannous glucoheptonate, stannous gluconate, stannous phosphonate, stannous chloride, and stannous fluoride.

### Claim 8 (depends on 5)

The peptide-based pharmaceutical composition of claim 5 wherein said composition further comprises a medically useful metal ion.

### Claim 9 (depends on 8)

The peptide-based pharmaceutical composition of claim 8 wherein said medically useful metal ion comprises a member selected from the group consisting of the elements iron, cobalt, nickel, copper, zinc, arsenic, selenium, technetium, ruthenium, palladium, silver, cadmium, indium, antimony, rhenium, osmium, iridium, platinum, gold, mercury, thallium, lead, bismuth, polonium and astatine.

### Claim 10 (depends on 8)

The peptide-based pharmaceutical composition of claim 8 wherein the medically useful metal ion is a radionuclide comprising an isotope selected from the group consisting of indium, gold, silver, mercury, technetium, rhenium and copper.

### Claim 11 (depends on 8)

The peptide-based pharmaceutical composition of claim 8 wherein the medically useful metal ion is radioactive.

### Claim 12 (depends on 1)

The peptide-based pharmaceutical composition of claim 1 wherein the composition is lyophilized.

### Claim 13

A high-affinity chemotactic peptide-based pharmaceutical composition suitable for administration to a patient comprising:
a biological-function domain; and
a medically useful metal ion-binding domain;
wherein said composition is selected from the group consisting of
(R.sub.1)--›Y.sub.1 !.sub.n --(R.sub.2),
(R.sub.1)--›Y.sub.1 --(R.sub.2)--Y.sub.1 !.sub.n --(R.sub.3)
and (R.sub.1)--›Y.sub.1 --(R.sub.2)--Y.sub.2 !.sub.n --(R.sub.3)
wherein the medically useful metal ion-binding domain is, respectively, ›Y.sub.1 !.sub.n, ›Y.sub.1 --(R.sub.2)--Y.sub.1 !.sub.n and ›Y.sub.1 --(R.sub.2)--Y.sub.2 !.sub.n in which n is a number between 1 and about 6 and Y.sub.1 and Y.sub.2 are amino acids comprising a sulfur, nitrogen or oxygen which is available for binding to a metal ion;
wherein the biological-function domain comprises at least one, or a portion of one, of the group consisting of amino acid sequences R.sub.1, R.sub.2 and R.sub.3, which comprises at least two linked N-formyl-Met-Leu-Phe sequences;
wherein those portions of R.sub.1, R.sub.2 and R.sub.3 not comprising the biological-function domain each comprise an amino acid sequence containing from 0 to about 20 amino acids;
wherein said medically useful metal ion-binding domain comprises at least one amino acid sequence consisting of at least one amino acid selected from the group consisting of cysteine, cystine, histidine, penicillamine, deacylated methionine, lysine, arginine, aspartic acid, glutamic acid, tyrosine, ›Cys!.sub.n, ›Cys--(R.sub.2)--Cys!.sub.n, ›Cys--(R.sub.2)--Pen!.sub.n, ›His--(R.sub.2)--Cys!.sub.n, ›His--(R.sub.2)--Pen!.sub.n, ›His!.sub.n and ›His--(R.sub.2)--His!.sub.n,
wherein n is a number between 1 and about 6; and R.sub.2 is independently an amino acid sequence containing from 1 to about 20 amino acids.