# US 5,705,143 A · Biological targeting agents > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,705,143 A - Document ID: US5705143A - Status: Granted - Kind: A - Application number: 08/676,263 - Filed: 1996-07-11 - Granted: 1998-01-06 - Earliest claimed: 1994-01-12 - Assignees: Amersham International plc - Inventors: Gary Robert Bower; Alan Michael Forster; Anthony Leonard Mark Riley; Anthony Eamon Storey - Web page: https://patentgrep.com/patent/US5705143A ## CPC - C07K 14/6555: {at least 1 amino acid in D-form} - A61K 51/083: {the peptide being octreotide or a somatostatin-receptor-binding peptide} - A61K 51/088: {conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10)} - 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) ## Abstract A conjugate comprises a linear or cyclic synthetic peptide of 3-50 amino acids linked via one of its carboxyl groups and optionally via a linking group, to a polydentate metal chelating group, with the result that endo- or exo-peptidase metabolism of the peptide is substantially inhibited, with the provisos that: a) the peptide chain contains a biological targeting sequence which is biologically active; b) when the spacer is absent the metal chelating group does not comprise solely peptide moieties; c) the metal chelating group does not contain thiol donors. A complex of the conjugate with a metal atom chelated by the metal chelating group is useful in medicine. ## Claims ### Claim 1 A conjugate comprising a linear or cyclic synthetic peptide of 3-50 amino acids linked via one of its carboxyl groups and optionally via a linking group, to a polydentate metal chelating group, with the result that endo- or exo-peptidase metabolism of the peptide is substantially inhibited, with the provisos that: a) the peptide chain contains a biological targeting sequence which is biologically active; b) when the linking group is absent the metal chelating group does not comprise solely peptide moieties; c) the metal chelating group does not contain thiol donors. ### Claim 2 (depends on 1) A conjugate as claimed in claim 1 of formula: (peptide--(CO)NR--(A).sub.p).sub.q --L where: L is the metal chelating group p is 0 to 10 q is 1 to 3; A is the same or different and is independently selected from the group consisting of --(CR.sub.2)--, --(CO)NR--, --NR(CO)--, --CR.dbd.CR--, and --CR.sub.2 QCR.sub.2 -- wherein Q is --O--, -S-- or --(NR)--, with the proviso that (A).sub.p contains a backbone chain of 10 atoms or less; R is independently H, C.sub.1-6 linear or branched hydrocarbon which may be alkyl or one or more of alkenyl; alkoxy; alkoxyalkyl; primary, secondary or tertiary amide; primary, secondary or tertiary amine; hydroxy; hydroxyalkyl; carboxylic acid; aryl or heteroaryl or two R groups taken together with the atoms to which they are attached form a carbocyclic, heterocyclic, saturated or unsaturated ring. ### Claim 3 (depends on 1) The conjugate as claimed in claim 1 wherein the metal chelating group is tetradentate. ### Claim 4 (depends on 1) A conjugate as claimed in claim 1 wherein the metal chelating group is a diaminedioxime of formula: ##STR8## where R is independently H, C.sub.1-6 linear or branched hydrocarbon which may be alkyl or one or more of alkenyl; alkoxy; alkoxyalkyl; primary, secondary or tertiary amide; primary, secondary or tertiary amine; hydroxy; hydroxyalkyl; carboxylic acid; aryl or heteroaryl or two R groups taken together with the atoms to which they are attached form a carbocyclic, heterocyclic, saturated or unsaturated ring; and n is 2 to 5 m is 1 or 2 with the provisos that: one or both of the amine groups may be an amide donor; 1to 3 of the R groups is --(A).sub.p NR(CO)-peptide and A is the same or different and is independently selected from the group consisting of --(CR.sub.2)--, --(CO)NR--, --NR(CO)--, --CR.dbd.CR--, and --CR.sub.2 QCR.sub.2 -- wherein Q is --O--, --S-- or --(NR)--, with the proviso that (A).sub.p contains a backbone chain of 10 atoms or less. ### Claim 5 (depends on 1) A complex comprising a conjugate according to claim 1 and a metal atom chelated by the metal chelating group. ### Claim 6 (depends on 5) A pharmaceutical composition comprising the complex as claimed in claim 5. ### Claim 7 (depends on 1) A method of radioimaging in an animal comprising the steps of complexing the conjugate of claim 1 with a radiometal to form a complex, administering said complex to said animal and detecting the presence of said complex in said animal. ### Claim 8 (depends on 1) A method of preparing a medicament for radioimaging comprising the step of complexing the conjugate of claim 1 with a radiometal.