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WO1998045329A1 - Derives de peptides natriuretiques - Google Patents

Derives de peptides natriuretiques Download PDF

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Publication number
WO1998045329A1
WO1998045329A1 PCT/DK1998/000142 DK9800142W WO9845329A1 WO 1998045329 A1 WO1998045329 A1 WO 1998045329A1 DK 9800142 W DK9800142 W DK 9800142W WO 9845329 A1 WO9845329 A1 WO 9845329A1
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WO
WIPO (PCT)
Prior art keywords
natriuretic
group
derivative according
substituent
amino acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/DK1998/000142
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English (en)
Inventor
Per Olaf Huusfeldt
Kjeld Madsen
Liselotte Bjerre Knudsen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novo Nordisk AS
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Novo Nordisk AS
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Filing date
Publication date
Application filed by Novo Nordisk AS filed Critical Novo Nordisk AS
Priority to AU68208/98A priority Critical patent/AU6820898A/en
Publication of WO1998045329A1 publication Critical patent/WO1998045329A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/58—Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Cardionatrin; Cardiodilatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention relates to novel derivatives of ANP and BNP, and fragments or extensions thereof and analogues of such fragments and extensions which have a protracted profile of action and to methods of making and using them.
  • Polypeptides are widely used in medical practice, and since they can be produced by recombinant DNA technology it can be expected that their importance will increase also in the years to come.
  • native polypeptides or analogues thereof are used in therapy it is generally found that they have a high clearance.
  • a high clearance of a therapeutic agent is inconvenient in cases where it is desired to maintain a therapeutically effective blood level thereof over a prolonged period of time since repeated administrations will then be necessary.
  • a high clearance of a therapeutic agent is inconvenient in cases where it is desired to maintain a therapeutically effective blood level thereof over a prolonged period of time since repeated administrations will then be necessary.
  • a high clearance of a therapeutic agent is inconvenient in cases where it is desired to maintain a therapeutically effective blood level thereof over a prolonged period of time since repeated administrations will then be necessary.
  • a high clearance of a therapeutic agent is inconvenient in cases where it is desired to maintain a therapeutically effective blood level thereof over a prolonged period of time since repeated administrations will
  • peptides are characterized by having a central ring structure with a cysteine bridge. Upon metabolization the cysteine bridge and thereby the central core structure is disrupted leaving the peptides inactive. Surprisingly, we found that derivatization of the peptides with a hydrophobic group protected the peptides against metabolic breakdown and thus increased the duration of action considerably.
  • amino acid sequence of the peptides are:
  • the present invention relates to derivatives of atrial natriuretic peptide or brain natriuretic peptide.
  • the derivatives according to the invention have interesting pharmacological properties, in particular they have a more protracted profile of action than the parent peptides.
  • an analogue is used to designate a peptide wherein one or more amino acid residues of the parent peptide have been substituted by another amino acid residue and/or wherein one or more amino acid residues of the parent peptide have been deleted and/or wherein one or more amino acid residues have been added to the parent peptide.
  • derivative is used in the present text to designate a peptide in which one or more of the amino acid residues have been chemically modified, e.g. by alkylation, acylation, ester formation or amide formation.
  • a natriuretic derivative is used in the present text to designate a derivative of ANP or an analogue thereof or a derivative of BNP or an analogue thereof.
  • the parent peptide from which such a derivative is formally derived is in some places referred to as the "natriuretic moiety" of the derivative.
  • the present invention relates to a natriuretic derivative having a lipophilic substituent attached to any one amino acid residue.
  • the present invention relates to a nautriuretic derivative wherein the lipophilic substituent comprises from 4 to 40 carbon atoms, more preferred from 8 to 25 carbon atoms.
  • the present invention relates to a natriuretic derivative wherein a lipophilic substituent is attached to an amino acid residue in such a way that a carboxyl group of the lipophilic substituent forms an amide bond with an amino group of the amino acid residue.
  • the present invention relates to a natriuretic derivative wherein a lipophilic substituent is attached to an amino acid residue in such a way that an amino group of the lipophilic substituent forms an amide bond with a carboxyl group of the amino acid residue.
  • the present invention relates to a natriuretic derivative wherein a lipophilic substituent is attached to the parent polypeptide by means of a spacer.
  • the present invention relates to a natriuretic derivative wherein a lipophilic substituent is attached to the parent polypeptide by means of a spacer which is an unbranched alkane ⁇ , ⁇ -dicarboxylic acid group having from 1 to 7 methylene groups, preferably two methylene groups which spacer forms a bridge between an amino group of the parent polypeptide and an amino group of the lipophilic substituent.
  • a spacer which is an unbranched alkane ⁇ , ⁇ -dicarboxylic acid group having from 1 to 7 methylene groups, preferably two methylene groups which spacer forms a bridge between an amino group of the parent polypeptide and an amino group of the lipophilic substituent.
  • the present invention relates to a natriuretic derivative wherein a lipophilic substituent is attached to the parent polypeptide by means of a spacer which is an amino acid residue except Cys, or a dipeptide such as Gly-Lys.
  • the present invention relates to a natriuretic derivative wherein a lipophilic substituent is attached to the parent polypeptide by means of a spacer which is an amino acid residue except Cys, or is a dipeptide such as Gly-Lys and wherein a carboxyl group of the parent polypeptide forms an amide bond with an amino group of a Lys residue or a dipeptide containing a Lys residue, and the other amino group of the Lys residue or a dipeptide containing a Lys residue forms an amide bond with a carboxyl group of the lipophilic substituent.
  • a spacer which is an amino acid residue except Cys, or is a dipeptide such as Gly-Lys and wherein a carboxyl group of the parent polypeptide forms an amide bond with an amino group of a Lys residue or a dipeptide containing a Lys residue, and the other amino group of the Lys residue or a dipeptide containing a Lys residue forms an amide bond
  • the present invention relates to a natriuretic derivative wherein a lipophilic substituent is attached to the parent polypeptide by means of a spacer which is an amino acid residue except Cys, or is a dipeptide such as Gly-Lys and wherein an amino group of the parent polypeptide forms an amide bond with a carboxylic group of the amino acid or dipeptide spacer, and an amino group of the amino acid or dipeptide spacer forms an amide bond with a carboxyl group of the lipophilic substituent.
  • a spacer which is an amino acid residue except Cys, or is a dipeptide such as Gly-Lys
  • an amino group of the parent polypeptide forms an amide bond with a carboxylic group of the amino acid or dipeptide spacer
  • an amino group of the amino acid or dipeptide spacer forms an amide bond with a carboxyl group of the lipophilic substituent.
  • the present invention relates to a natriuretic derivative wherein a lipophilic substituent is attached to the parent polypeptide by means of a spacer which is an amino acid residue except Cys, or is a dipeptide such as Gly-Lys and wherein a carboxyl group of the parent polypeptide forms an amide bond with an amino group of the amino acid or dipeptide spacer, and the carboxyl group of the amino acid or dipeptide spacer forms an amide bond with an amino group of the lipophilic substituent.
  • the present invention relates to a natriuretic derivative wherein a lipophilic substituent is attached to the parent polypeptide by means of a spacer which is an amino acid residue except Cys, or is a dipeptide such as Gly-Lys, and wherein a carboxyl group of the parent polypeptide forms an amide bond with an amino group of Asp or Glu, or a dipeptide containing an Asp or Glu residue, and a carboxyl group of the spacer forms an amide bond with an arnino group of the lipophilic substituent.
  • a spacer which is an amino acid residue except Cys, or is a dipeptide such as Gly-Lys
  • the present invention relates to a natriuretic derivative having a lipophilic substituent which comprises a partially or completely hydrogenated cyclopentanophenathrene skeleton.
  • the present invention relates to a natriuretic derivative having a lipophilic substituent which is a straight-chain or branched alkyl group.
  • the present invention relates to a natriuretic derivative having a lipophilic substituent which is the acyl group of a straight-chain or branched fatty acid.
  • the present invention relates to a natriuretic derivative having a hpophilic substituent which is an acyl group selected from the group comprising CILXCH ⁇ CO-, wherein n is 4 to 38, preferably CH 3 (CH 2 ) 6 CO-, CILXCI JgCO-, CH 3 (CH 2 ) 10 CO-, CH 3 (CH 2 ) 12 CO-, CH 3 (CH 2 ) 14 CO-, CH 3 (CH 2 ) 16 CO-, CIL CH ⁇ CO-, CH 3 (CH 2 ) 20 CO- and CH 3 (CH 2 ) 22 CO-.
  • the present invention relates to a natriuretic derivative having a lipophilic substituent which is an acyl group of a straight-chain or branched alkane ⁇ , ⁇ - dicarboxylic acid.
  • the present invention relates to a natriuretic derivative having a hpophilic substituent which is an acyl group selected from the group comprising HOOC(CH 2 ) m CO-, wherein m is 4 to 38, preferably HOOC(CH 2 ) M CO-, HOOC(CH 2 ) 16 CO-, HOOC(CH 2 ) 18 CO-, HOOC(CH 2 ) 20 CO- and HOO CH ⁇ CO-.
  • a hpophilic substituent which is an acyl group selected from the group comprising HOOC(CH 2 ) m CO-, wherein m is 4 to 38, preferably HOOC(CH 2 ) M CO-, HOOC(CH 2 ) 16 CO-, HOOC(CH 2 ) 18 CO-, HOOC(CH 2 ) 20 CO- and HOO CH ⁇ CO-.
  • the present invention relates to a natriuretic derivative having a hpophilic substituent which is a group of the formula CH 3 (CH 2 ) p ((CH 2 ) q COOH)CHNH- CO(CH 2 ) 2 CO-, wherein p and q are integers and p+q is an integer of from 8 to 40, preferably from 12 to 35.
  • the present invention relates to a natriuretic derivative having a hpophilic substituent which is a group of the formula CH 3 (CH 2 ) r CO- NHCH(COOH)(CH 2 ) 2 CO-, wherein r is an integer of from 10 to 24.
  • the present invention relates to a natriuretic derivative having a hpophilic substituent which is a group of the formula CH 3 (CH 2 ) s CO- NHCH((CH 2 ) 2 COOH)CO-, wherein s is an integer of from 8 to 24.
  • the present invention relates to a natriuretic derivative having a lipophilic substituent which is a group of the formula COOH(CH 2 ) t CO- wherein t is an integer of from 8 to 24.
  • the present invention relates to a natriuretic derivative having a hpophilic substituent which is a group of the formula -NHCH(COOH)(CH 2 ) 4 NH- CO(CH 2 ) u CH 3 , wherein u is an integer of from 8 to 18.
  • the present invention relates to a natriuretic derivative having a lipophilic substituent which is a group of the formula -NHCH(COOH)(CH 2 ) 4 NH- COCH((CH 2 ) 2 COOH)NH-CO(CH 2 ) w CH 3 , wherein w is an integer of from 10 to 16.
  • the present invention relates to a natriuretic derivative having a hpophilic substituent which is a group of the formula -NHCH(COOH)(CH 2 ) 4 NH- CO(CH 2 ) 2 CH(COOH)NH-CO(CH 2 ) x CH 3 , wherein x is an integer of from 10 to 16.
  • the present invention relates to a natriuretic derivative having a hpophilic substituent which is a group of the formula -NHCH(COOH)(CH 2 ) 4 NH- CO(CH 2 ) 2 CH(COOH)NHCO(CH 2 ) y CH 3 , wherein y is zero or an integer of from 1 to 22.
  • the present invention relates to a natriuretic derivative which has one hpophilic substituent.
  • the present invention relates to a natriuretic derivative which has two lipophilic substituents.
  • the present invention relates to a natriuretic derivative in which the C-terminal amino acid residue is present in the form of the amide.
  • the present invention relates to a natriuretic derivative having a hpophilic substituent which can be negatively charged.
  • the present invention relates to the use of a natriuretic derivative, wherein the parent polypeptide is selected from the group comprising ANP- (1-28) or an analogue or a fragment thereof.
  • the present invention relates to the use of an ANP derivative, selected from the group comprising ANP-(2-28), ANP-(3-28), ANP-(4-28), ANP-(5-28) and ANP-(6-28) and an analogue thereof.
  • the present invention relates to the use of an ANP derivative, selected from the group comprising ANP-(l-28)-Pro 29 -amide and an analogue thereof.
  • the present invention relates to the use of an ANP derivative, wherein the designation analogue comprises derivatives wherein 1-15, preferably 1-10 amino acid residues have been exchanged with any -amino acid residue, in particular lys.
  • the present invention relates to the use of a natriuretic derivative, wherein the parent polypeptide is selected from the group comprising BNP- (1-32) or an analogue or a fragment thereof.
  • the present invention relates to the use of a BNP derivative, selected from the group comprising BNP-(2-32), BNP-(3-32), BNP-(4-32), BNP-(5-32) , BNP- (6-32), BNP-(7-32), BNP-(8-32) and BNP-(9-32) and an analogue thereof.
  • a BNP derivative selected from the group comprising BNP-(2-32), BNP-(3-32), BNP-(4-32), BNP-(5-32) , BNP- (6-32), BNP-(7-32), BNP-(8-32) and BNP-(9-32) and an analogue thereof.
  • the present invention relates to the use of a BNP derivative, wherein the designation analogue comprises derivatives wherein 1-15, preferably 1-10 amino acid residues have been exchanged with any ⁇ -amino acid residue, in particular lys.
  • the present invention relates to the use of a pharmaceutical composition comprising a natriuretic derivative and a pharmaceutically acceptable vehicle or carrier as described in International Patent Application WO90/01940 (Scios Nova Inc.) and in European Patent Application EP 269299 (Novo Nordisk A/S).
  • the present invention relates to the use of a natriuretic derivative for the preparation of a medicament with protracted effect.
  • the present invention relates to the use of a natriuretic derivative for the preparation of a medicament with protracted effect for the treatment of hypertension.
  • the present invention relates to the use of a natriuretic derivative for the preparation of a medicament with protracted effect for the treatment of congestive heart failure.
  • the present invention relates to the use of a natriuretic derivative according to for the preparation of a medicament with protracted effect for the treatment of diseases in the renal function.
  • the present invention relates to the use of a natriuretic for the preparation of a medicament with protracted effect for the treatment of oedema.
  • the present invention relates to the use of a natriuretic derivative for the preparation of a medicament with protracted effect for the treatment of hepatic cirrhosis.
  • the hpophilic substituent attached to the natriuretic moiety preferably comprises 4-40 carbon atoms, in particular 8-25 carbon atoms.
  • the hpophilic substituent may be attached to an amino group of the natriuretic moiety by means of a carboxyl group of the lipophilic substituent which forms an amide bond with an amino group of the amino acid to which it is attached.
  • the hpophilic substituent may be attached to said amino acid in such a way that an amino group of the lipophilic substituent forms an amide bond with a carboxyl group of the amino acid.
  • the lipophililic substituent may be linked to the natriuretic moiety via an ester bond.
  • the ester can be formed either by reaction between a carboxyl group of the natriuretic moiety and a hydroxyl group of the substituent-to-be or by reaction between a hydroxyl group of the natriuretic moiety and a carboxyl group of the substituent-to-be.
  • the hpophilic substituent can be an alkyl group which is introduced into a primary amino group of the natriuretic moiety.
  • the lipophilic substituent is attached to the natriuretic moiety by means of a spacer in such a way that a carboxyl group of the spacer forms an amide bond with an amino group of the natriuretic moiety.
  • suitable spacers are succinic acid, Lys, Glu or Asp, or a dipeptide such as Gly-Lys.
  • the spacer is succinic acid, one carboxyl group thereof may form an amide bond with an amino group of the amino acid, and the other carboxyl group thereof may form an amide bond with an amino group of the hpophilic substituent.
  • the spacer is Lys, Glu or Asp
  • the carboxyl group thereof may form an amide bond with an amino group of the amino acid
  • the amino group thereof may form an amide bond with a carboxyl group of the lipophilic substituent.
  • a further spacer may in some instances be inserted between the ⁇ -amino group of Lys and the lipophilic substituent.
  • such a further spacer is succinic acid which forms an amide bond with the ⁇ -amino group of Lys and with an amino group present in the hpophilic substituent.
  • such a further spacer is Glu or Asp which forms an amide bond with the ⁇ -amino group of Lys and another amide bond with a carboxyl group present in the hpophilic substituent, that is, the hpophilic substituent is a N ⁇ acylated lysine residue.
  • the hpophilic substituent has a group which can be negatively charged.
  • One prefened group which can be negatively charged is a carboxylic acid group.
  • the parent polypeptide can be produced by a method which comprises culturing a host cell containing a DNA sequence encoding the polypeptide and capable of expressing the polypeptide in a suitable nutrient medium under conditions permitting the expression of the polypeptide, after which the resulting polypeptide is recovered from the culture.
  • the medium used to culture the cells may be any conventional medium suitable for growing the host cells, such as minimal or complex media containing appropriate supplements. Suitable media are available from commercial suppliers or may be prepared according to published recipes (e.g. in catalogues of the American Type Culture Collection).
  • the polypeptide produced by the cells may then be recovered from the culture medium by conventional procedures including separating the host cells from the medium by centrifugation or filtration, precipitating the proteinaceous components of the supernatant or filtrate by means of a salt, e.g. ammonium sulphate, purification by a variety of chromatographic procedures, e.g. ion exchange chromatography, gelfiltration chromatography, affinity chromatography, or the like, dependent on the type of polypeptide in question.
  • a salt e.g. ammonium sulphate
  • the DNA sequence encoding the parent polypeptide may suitably be of genomic or cDNA origin, for instance obtained by preparing a genomic or cDNA library and screening for DNA sequences coding for all or part of the polypeptide by hybridization using synthetic oligonucleotide probes in accordance with standard techniques (see, for example, Sambrook, J, Fritsch, EF and Maniatis, T, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, New York, 1989).
  • the DNA sequence encoding the polypeptide may also be prepared synthetically by established standard methods, e.g.
  • the DNA sequence may also be prepared by polymerase chain reaction using specific primers, for instance as described in US 4,683,202 or Saiki et al. , Science 239 (1988), 487 - 491.
  • the DNA sequence may be inserted into any vector which may conveniently be subjected to recombinant DNA procedures, and the choice of vector will often depend on the host cell into which it is to be introduced.
  • the vector may be an autonomously replicating vector, i.e. a vector which exists as an extrachromosomal entity, the replication of which is independent of chromosomal replication, e.g. a plasmid.
  • the vector may be one which, when introduced into a host cell, is integrated into the host cell genome and replicated together with the chromosome(s) into which it has been integrated.
  • the vector is preferably an expression vector in which the DNA sequence encoding the polypeptide is operably linked to additional segments required for transcription of the DNA, such as a promoter.
  • the promoter may be any DNA sequence which shows transcriptional activity in the host cell of choice and may be derived from genes encoding proteins either homologous or heterologous to the host cell. Examples of suitable promoters for directing the transcription of the DNA encoding the polypeptide of the invention in a variety of host cells are well known in the art, cf. for instance Sambrook et al.. , supra.
  • the DNA sequence encoding the polypeptide may also, if necessary, be operably connected to a suitable terminator, polyadenylation signals, transcriptional enhancer sequences, and translational enhancer sequences.
  • the recombinant vector of the invention may further comprise a DNA sequence enabling the vector to replicate in the host cell in question.
  • the vector may also comprise a selectable marker, e.g. a gene the product of which complements a defect in the host cell or one which confers resistance to a drug, e.g. ampicillin, kanamycin, tetracyclin, chloramphenicol, neomycin, hygromycin or methotrexate.
  • a selectable marker e.g. a gene the product of which complements a defect in the host cell or one which confers resistance to a drug, e.g. ampicillin, kanamycin, tetracyclin, chloramphenicol, neomycin, hygromycin or methotrexate.
  • a secretory signal sequence (also known as a leader sequence, prepro sequence or pre sequence) may be provided in the recombinant vector.
  • the secretory signal sequence is joined to the DNA sequence encoding the polypeptide in the conect reading frame.
  • Secretory signal sequences are commonly positioned 5 1 to the DNA sequence encoding the polypeptide.
  • the secretory signal sequence may be that normally associated with the polypeptide or may be from a gene encoding another secreted protein.
  • the host cell into which the DNA sequence or the recombinant vector is introduced may be any cell which is capable of producing the present polypeptide and includes bacteria, yeast, fungi and higher eukaryotic cells.
  • suitable host cells well known and used in the art are, without limitation, E. coli, Saccharomyces cerevisiae, or mammalian BHK or CHO cell lines.
  • the nautriuretic derivatives can be produced according to the procedures described in the international patent application WO 96/29342.
  • natriuretic analogues are described in Euoropean Patent Application EP 269299 (Novo Nordisk A/S) which relates to derivatives of ANP wherein at least two of the amino acid residues in ring structure (Positions 7-23) are exchanged with other amino acid residues and/or which in the C-terminal end (Position 28) are elongated with Pro, Tip, Phe or N-MePhe or a polypeptide moiety having one of the last mentioned four amino acid residues in the N-terminal end, have improved pharmacological properties.
  • compositions containing a polypeptide derivative according to the present invention may be administered parenterally to patients in need of such a treatment.
  • Parenteral administration may be performed by subcutaneous, intramuscular or intravenous injection by means of a syringe, optionally a pen-hke syringe.
  • parenteral administration can be performed by means of an infusion pump.
  • a further option is a composition which may be a powder or a liquid for the administration of the polypeptide derivative in the form of a nasal or pulmonal spray.
  • the polypeptide derivatives of the invention can also be administered transdermally, e.g. from a patch, optionally a iontophoretic patch.
  • compositions containing a polypeptide derivative of the present invention may be prepared by conventional techniques, e.g. as described in Remington's Pharmaceutical Sciences. 5 1985.
  • the injectable compositions of the polypeptide derivative of the invention can be prepared using the conventional techniques of the pharmaceutical industry which involves dissolving and mixing the ingredients as appropriate to give the desired end product.
  • the polypeptide derivative is dissolved in an amount of water which is somewhat less than the final volume of the composition to be prepared.
  • An isotonic agent, a preservative and a buffer is added as required and the pH value of the solution is adjusted - if necessary - using an acid, e.g. hydrochloric acid, or a base, e.g. aqueous sodium 5 hydroxide as needed. FinaUy, the volume of the solution is adjusted with water to give the desired concentration of the ingredients.
  • isotonic agents sodium chloride, mannitol and glycerol.
  • preservatives are phenol, m-cresol, methyl p-hydroxybenzoate and benzyl alcohol.
  • Suitable buffers are sodium acetate and sodium phosphate.
  • composition for nasal administration of certain polypeptides may, for example, be prepared as 5 described in European Patent No. 272097 (to Novo Nordisk A/S) or in WO 93/18785.
  • the natriuretic derivative is provided in the form of an injectable solution.
  • the solutions preferably contain not less than about 2 mg/ml, preferably not less than about 5 mg/ml, more prefened not less than 30 about 10 mg/ml of the natriureticl derivative and, preferably, not more than about 100 mg/ml of the natriureticl derivative.
  • the polypeptide derivatives of this invention can be used in the treatment of various diseases.
  • polypeptide derivative to be used and the optimal dose level for any patient will depend on the disease to be treated and on a variety of factors including the efficacy of the specific peptide derivative employed, the age, body weight, physical activity, and diet of the patient, on a possible combination with other drugs, and on the severity of the case. It is recommended that the dosage of the polypeptide derivative of this invention be determined for each individual patient by those skilled in the art in a similar way as for known parent polypeptides.
  • the derivatized natriuretic derivative will be useful for the preparation of a medicament with protracted action/effect for the treatment of renal diseases and/or for the treatment of hypertension and/or for the treatment of congestive heart failure.

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Abstract

L'invention concerne des dérivés d'ANP (peptide natriurétique auriculaire) et de BNP (peptide natriurétique du cerveau) et leurs analogues possédant un substituant lipophile, qui présentent des propriétés pharmacologiques intéressantes. En particulier, ces dérivés ont un profil d'action plus prolongée que les peptides parents.
PCT/DK1998/000142 1997-04-04 1998-04-06 Derives de peptides natriuretiques Ceased WO1998045329A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU68208/98A AU6820898A (en) 1997-04-04 1998-04-06 Natriuretic peptide derivatives

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US4340097P 1997-04-04 1997-04-04
US60/043,400 1997-04-04

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WO1998045329A1 true WO1998045329A1 (fr) 1998-10-15

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006076471A3 (fr) * 2005-01-12 2007-03-22 Nobex Corp Conjugues bnp et procedes d'utilisation
EP1776132A4 (fr) * 2004-05-26 2009-07-01 Biocon Ltd Composes natriuretiques, leurs conjugues, et utilisation de ceux-ci
US7662773B2 (en) 2002-11-26 2010-02-16 Biocon Limited Natriuretic compounds, conjugates, and uses thereof
US7754852B2 (en) * 2007-07-20 2010-07-13 Mayo Foundation For Medical Education And Research Natriuretic polypeptides
US8058242B2 (en) 2004-07-15 2011-11-15 The University Of Queensland Chimeric proteins with natriuretic activity
US8710006B2 (en) 2005-04-07 2014-04-29 Cardiopep Pharma Gmbh Use of natriuretic peptide for treating heart failure
US9102707B2 (en) 2011-08-30 2015-08-11 Mayo Foundation For Medical Education And Research Natriuretic polypeptides
US9611305B2 (en) 2012-01-06 2017-04-04 Mayo Foundation For Medical Education And Research Treating cardiovascular or renal diseases
WO2024086680A2 (fr) 2022-10-21 2024-04-25 Eli Lilly And Company Peptides natriurétiques à action prolongée et leurs utilisations

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1987002674A1 (fr) * 1985-11-05 1987-05-07 Biotechnology Research Associates, J.V. Analogues de peptides atriaux natriuretiques
WO1989009611A1 (fr) * 1988-03-29 1989-10-19 California Biotechnology Inc. Analogues cycliques de peptides natriuretiques atriaux
WO1995013296A1 (fr) * 1993-11-12 1995-05-18 Genentech, Inc. Peptides natriuretiques auriculaires specifiques d'un recepteur

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1987002674A1 (fr) * 1985-11-05 1987-05-07 Biotechnology Research Associates, J.V. Analogues de peptides atriaux natriuretiques
WO1989009611A1 (fr) * 1988-03-29 1989-10-19 California Biotechnology Inc. Analogues cycliques de peptides natriuretiques atriaux
WO1995013296A1 (fr) * 1993-11-12 1995-05-18 Genentech, Inc. Peptides natriuretiques auriculaires specifiques d'un recepteur

Cited By (19)

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JP2010534062A (ja) * 2007-07-20 2010-11-04 メイヨ・ファウンデーション・フォー・メディカル・エデュケーション・アンド・リサーチ ナトリウム利尿ポリペプチド
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