.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 6,086,849

« Back to Dashboard

Details for Patent: 6,086,849

Title: Technetium-99m labeled peptides for imaging
Abstract:This invention relates to radiolabeled peptides and methods for producing such peptides. Specifically, the invention relates to peptides, methods and kits for making such peptides, and methods for using such peptides to image sites in a mammalian body labeled with technetium-99m (Tc-99m) via a radiolabel-binding moiety which forms a neutral complex with Tc-99m.
Inventor(s): Dean; Richard T. (Bedford, NH), Buttram; Scott (Derry, NH), McBride; William (Manchester, NH), Lister-James; John (Bedford, NH), Civitello; Edgar R. (Merrimack, NH)
Assignee: Diatide, Inc. (Londonderry, NH)
Filing Date:Feb 09, 1995
Application Number:08/170,299
Claims:1. A reagent for preparing a scintigraphic imaging agent, said reagent comprising a specific binding peptide having from about three to about 100 amino acids and being covalently linked to a radiolabel-binding moiety that forms an electrically neutral complex when bound to a radioisotope.

2. The reagent of claim 1, wherein the peptide and the moiety are covalently linked through from about one to about 20 amino acids.

3. The reagent of claim 1 wherein the radioisotope is technetium-99m.

4. The reagent of claim 1 wherein the peptide is selected from the group consisting of peptides having the amino acid sequences:

formyl-MLF

(VGVAPG).sub.3 amide

(VPGVG).sub.4 amide

RALVDTLKFVTQAEGAKamide (SEQ ID No.:1)

RALVDTEFKVKQEAGAKamide (SEQ ID No.:2)

PLARITLPDFRLPEIAIPamide (SEQ ID No.:3)

GQQHHLGGAKAGDV (SEQ ID No.:4)

PLYKKIIKKLLES (SEQ ID No.:5)

LRALVDTLKamide (SEQ ID No.:6)

GGGLRALVDTLKamide (SEQ ID No.:7)

GGGLRALVDTLKFVTQAEGAKamide (SEQ ID No.:8)

GGGRALVDTLKALVDTLamide (SEQ ID No.:9)

GHRPLDKKREEAPSLRPAPPPISGGGYR (SEQ ID No.:10)

PSPSPIHPAHHKRDRRQamide (SEQ ID No.:11)

GGGF.sub.D.Cpa.YW.sub.D KTFTamide (SEQ ID No.:12) ##STR6## (SYNRGDSTC).sub.3 -TSEA GGGLRALVDTLKamide (SEQ ID No.:14)

GCGGGLRALVDTLKamide (SEQ ID No.:15)

GCYRALVDTLKFVTQAEGAKamide (SEQ ID No.:16) and

GC(VGVAPG).sub.3 amide.

5. A reagent for preparing a scintigraphic imaging agent comprising:

a) at least two specific binding peptides, each having an amino acid sequence of from about1 three to about 100 amino acids;

b) at least one radiolabel binding moiety capable of forming an electrically neutral complex with a radioisotope; and

c) a polyvalent linking moiety covalently linked to the peptides and to the radiolabel binding moiety, thereby forming a multimer,

wherein the molecular weight of the reagent is less than about 20,000 daltons.

6. The reagent of claim 5 wherein the polyvalent linking moiety is bis-succinimidylmethylether, 4-(2,2-dimethylacetyl)benzoic acid, N-[2-(N',N'-bis(2-succinimidoethyl)aminoethyl)]-N.sup.6,N.sup.9 -bis(2-methyl-2-mercaptopropyl)-6,9-diazanonanamide, tris(succinimidylethyl)amine or a derivative thereof.

7. A scintigraphic imaging agent comprising the reagent of claim 1, wherein the moiety is bound to a radiolabel.

8. The agent of claim 7, wherein the radiolabel is technetium-99m.

9. A process of preparing the reagent of claim 1, wherein the peptide is chemically synthesized in vitro.

10. The process of claim 9, wherein the peptide is synthesized by solid phase peptide synthesis.

11. A reagent for preparing a scintigraphic imaging agent, said reagent comprising a specific binding peptide having from about 3 to about 100 amino acids and being covalently linked to a radiolabel-binding moiety of formula: ##STR7## wherein X=H or a protecting group;

(amino acid)=any amino acid;

and wherein the moiety forms an electrically neutral complex when bound to a radioisotope.

12. The reagent of claim 11, wherein (amino acid) is glycine and X is an acetamidomethyl protecting group.

13. The reagent of claim 11, wherein the peptide and the moiety are covalently linked through from about one to about 20 amino acids.

14. The reagent of claim 11 wherein the radioisotope is technetium-99m.

15. The reagent of claim 11, wherein the peptide is selected from the group consisting of:

formyl-MLF

(VGVAPG).sub.3 amide

(VPGVG).sub.4 amide

RALVDTLKFVTQAEGAKamide (SEQ ID No.:1)

RALVDTEFKVKQEAGAKamide (SEQ ID No.:2)

PLARITLPDFRLPEIAIPamide (SEQ ID No.:3)

GQQHHLGGAKAGDV (SEQ ID No.:4)

PLYKKIIKKLLES (SEQ ID No.:5)

LRALVDTLKamide (SEQ ID No.:6)

GGGLRALVDTLKamide (SEQ ID No.:7)

GGGLRALVDTLKFVTQAEGAKamide (SEQ ID No.:8)

GGGRALVDTLKALVDTLamide (SEQ ID No.:9)

GHRPLDKKREEAPSLRPAPPPISGGGYR (SEQ ID No.:10)

PSPSPIHPAHHKRDRRQamide (SEQ ID No.:11)

GGGF.sub.D.Cpa.YW.sub.D KTFTamide (SEQ ID No.:12) ##STR8## (SYNRGDSTC).sub.3 -TSEA GGGLRALVDTLKamide (SEQ ID No.:14)

GCGGGLRALVDTLKamide (SEQ ID No.:15)

GCYRALVDTLKFVTQAEGAKamide (SEQ ID No.:16) and

GC(VGVAPG).sub.3 amide.

16. The reagent of claim 5, wherein the radiolabel-binding moiety is selected from the group consisting of: ##STR9## wherein X=H or a protecting group;

(amino acid)=any amino acid; ##STR10## wherein X=H or a protecting group;

(amino acid)=any amino acid; ##STR11## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 ;

each (pgp).sup.S is independently a thiol protecting group or H;

m, n and p are independently 2 or 3;

A=linear lower alkyl, cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof; and

##STR12## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 ;

m, n and p are independently 2 or 3;

A=linear lower alkyl, cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof;

V=H or --CO-peptide;

R'=H or peptide;

and wherein when V=H, R'=peptide and when R'=H, V=--CO-peptide.

17. The reagent of claim 16, wherein the polyvalent linking moiety is bis-succinimidylmethylether, 4-(2,2-dimethylacetyl)benzoic acid, N-[2-(N',N'-bis(2-succinimido-ethyl)aminoethyl)]-N.sup.6,N.sup.9 -bis(2-methyl-2-mercaptopropyl)-6,9-diazanonanamide, tris(succinimidylethyl)amine or a derivative thereof.

18. A scintigraphic imaging agent comprising the reagent of claim 11, wherein the moiety is bound to a radiolabel.

19. The agent of claim 18, wherein the radiolabel is technetium-99m.

20. A process of preparing the reagent of claim 11, wherein the peptide is chemically synthesized in vitro.

21. The process of claim 20, wherein the peptide is synthesized by solid phase peptide synthesis.

22. A reagent for preparing an scintigraphic imaging agent, said reagent comprising a specific binding peptide having from about 3 to about 100 amino acids, and being covalently linked to a radiolabel-binding moiety, wherein the moiety forms an electrically neutral complex when bound to a radioisotope, said moiety having a formula selected from the group consisting of: ##STR13## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 ;

each (pgp).sup.S is independently a thiol protecting group or H;

m, n and p are independently 2 or 3;

A=linear lower alkyl, cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof; and ##STR14## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 ;

m, n and p are independently 2 or 3;

A=linear lower alkyl, cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof;

V=H or --CO-peptide;

R'=H or peptide;

and wherein when V=H, R'=peptide and when R'=H, V=--CO-peptide.

23. The reagent of claim 22, wherein the peptide and the moiety are covalently linked through from about one to about 20 amino acids.

24. The reagent of claim 22, wherein the radioisotope is technetium-99m.

25. The reagent of claim 22, wherein the peptide is selected from the group consisting of:

formyl-MLF

(VGVAPG).sub.3 amide

(VPGVG).sub.4 amide

RALVDTLKFVTQAEGAKamide (SEQ ID No.:1)

RALVDTEFKVKQEAGAKamide (SEQ ID No.:2)

PLARITLPDFRLPEIAIPamide (SEQ ID No.:3)

GQQHHLGGAKAGDV (SEQ ID No.:4)

PLYKKIIKKLLES (SEQ ID No.:5)

LRALVDTLKamide (SEQ ID No.:6)

GGGLRALVDTLKamide (SEQ ID No.:7)

GGGLRALVDTLKFVTQAEGAKamide (SEQ ID No.:8)

GGGRALVDTLKALVDTLamide (SEQ ID No.:9)

GHRPLDKKREEAPSLRPAPPPISGGGYR (SEQ ID No.:10)

PSPSPIHPAHHKRDRRQamide (SEQ ID No.:11)

GGGF.sub.D.Cpa.YW.sub.D KTFTamide (SEQ ID No.:12) ##STR15## (SYNRGDSTC).sub.3 -TSEA GGGLRALVDTLKamide (SEQ ID No.:14)

GCGGGLRALVDTLKamide (SEQ ID No.:15)

GCYRALVDTLKFVTQAEGAKamide (SEQ ID No.:16) and

GC(VGVAPG).sub.3 amide.

26. A scintigraphic imaging agent comprising the reagent of claim 22, wherein the moiety is bound to a radiolabel.

27. The agent of claim 26, wherein the radiolabel is technetium-99m.

28. A process of preparing the reagent of claim 22, wherein the peptide is chemically synthesized in vitro.

29. The process of claim 28, wherein the peptide is synthesized by solid phase peptide synthesis.

30. A composition comprising an .epsilon.-amino group of a N-.alpha.-protected lysine attached to a radiolabel-binding moiety having a formula selected from the group consisting of: ##STR16## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 but if X=H, one R=Y;

(pgp).sub.N =an amine protecting group or H;

each (pgp).sup.S is independently a thiol protecting group or H;

m, n and p are independently 2 or 3;

X=H or --A--COOH, but if X=H, one R=Y and (pgp).sub.N is not H;

Y=--A--COOH;

A=linear lower alkyl, cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof; ##STR17## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 but if Z=H, one R=Y;

each (pgp).sub.N is an amine protecting group or H;

each (pgp).sup.S is independently a thiol protecting group or H;

m, n and p are independently 2 or 3;

Z=H or --A--CH(V)NH(pgp).sub.2.sup.N, but if Z=H, one R=Y;

Y=--A--CH(V)NH(pgp).sub.2.sup.N ;

A=linear lower alkyl, cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof;

V=H or COOH;

and wherein if (pgp).sub.1.sup.N and V are H, then (pgp).sup.S is not H and if (pgp).sup.S and V are H, then (pgp).sup.N is not H, and if V is H, (pgp).sub.1.sup.N is not H; and ##STR18## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 and one R=Y;

each (pgp).sup.N is an amine protecting group or H;

each (pgp).sup.S is independently a thiol protecting group or H;

m, n and p are independently 2 or 3;

Y=--A--CH(V)NH(pgp).sub.2.sup.N ;

A=linear or cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof;

V=H or COOH;

and wherein if (pgp).sub.2.sup.N and V are H, then (pgp).sup.S is not H and if (pgp).sup.S and V are H, then (pgp).sub.2.sup.N is not H, and at least one (pgp).sub.1.sup.N moiety is not H.

31. A composition comprising [N-.epsilon.-(N.sup.9 -t-butoxycarbonyl)-N.sup.6,N.sup.9 -bis[2-methyl-2-(triphenylmethylthio)propyl]-6,9-diazanonanoyl)-N-.alpha.- Fmoc-lysine.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc