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WO1998000536A1 - Methodes immunocontraceptives et peptide ou polypeptides a utiliser dans lesdites methodes - Google Patents

Methodes immunocontraceptives et peptide ou polypeptides a utiliser dans lesdites methodes Download PDF

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Publication number
WO1998000536A1
WO1998000536A1 PCT/GB1997/001740 GB9701740W WO9800536A1 WO 1998000536 A1 WO1998000536 A1 WO 1998000536A1 GB 9701740 W GB9701740 W GB 9701740W WO 9800536 A1 WO9800536 A1 WO 9800536A1
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WO
WIPO (PCT)
Prior art keywords
peptide
polypeptide
uteroglobin
mammal
fragment
Prior art date
Application number
PCT/GB1997/001740
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English (en)
Inventor
Michael John Taussig
Derek Bryan Alfred Symons
Original Assignee
The Minister Of Agriculture, Fisheries And Food In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by The Minister Of Agriculture, Fisheries And Food In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland filed Critical The Minister Of Agriculture, Fisheries And Food In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland
Priority to AU33500/97A priority Critical patent/AU3350097A/en
Priority to CA002259237A priority patent/CA2259237A1/fr
Publication of WO1998000536A1 publication Critical patent/WO1998000536A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/0005—Vertebrate antigens
    • A61K39/0006—Contraceptive vaccins; Vaccines against sex hormones
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4715—Pregnancy proteins, e.g. placenta proteins, alpha-feto-protein, pregnancy specific beta glycoprotein
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031—Proteins
    • A61K2039/6081—Albumin; Keyhole limpet haemocyanin [KLH]

Definitions

  • the present invention relates to contraceptive methods effective in mammals and particularly rabbits, to peptides and polypeptides which are useful in those methods, to processes for their production and to pharmaceutical compositions containing them.
  • a contraceptive vaccine particularly for wild or feral species of mammals such as wild rabbits, would be desirable in order to achieve a level of control over the population levels of these mammals.
  • Uteroglobin is the predominant protein in the uterine lumen of rabbits during the pre- implantation phase of pregnancy, accounting for up to 40-50% of the protein content of the uterine secretion in early pregnancy. It is a secreted protein of MW 14kD comprising a dimer of two identical chains of 70 amino acids, linked by disulphide bridges. The structure has been fully characterised (Morize I et al., J. Mol. Biol. (1987) 194: 725-739) and comprises three helical regions interconnected by interhelical loops ( Figure 1).
  • UG Several properties of UG have been identified, including binding of progesterone, inhibition of inflammation and immunosuppressive effects by masking the antigenicity of sperm and embryos within the female tract.
  • an immune response can be stimulated in mammals such as rabbits, against uteroglobin or to polypeptides or small peptides based upon uteroglobin. Furthermore, it has been found that the response can inhibit fertility of the mammal so giving rise to an immunocontraceptive.
  • the present invention provides a method for controlling the fertility of a female mammal, said method comprising administering to said mammal an agent which stimulates an immune response, wherein the response includes the production of an element which interacts with uteroglobin of said mammal so as to reduce the fertility thereof.
  • Suitable agents for use in the method comprises a peptide or polypeptide which stimulates an immune response, said response including production of a binding element which specifically binds uteroglobin so as to reduce fertility of said female mammal or an expression vector which encodes a such a peptide or polypeptide and expresses said peptide or polypeptide in vivo in said mammal.
  • polypeptide' is intended to encompass proteins.
  • Binding elements will generally comprise immunoglobulins and in particular antibodies. In order to achieve a contraceptive effect, it may be necessary to deliver the peptide or polypeptide using an appropriate delivery strategy as is conventional in the art.
  • the method will comprise administration of a peptide or polypeptide which stimulates an immune response, said response including production of a binding element which bind uteroglobin and reduce fertility of said female mammal.
  • Novel peptides or polypeptides for use in this method which are able to stimulate an immune response in a mammal, said response having an effect on uteroglobin so as to reduce the fertility of a female mammal, form a further aspect of the invention.
  • the peptide or polypeptide comprises uteroglobin or a fragment thereof, or a variant or peptide mimetic of any of these, which is coupled to a carrier protein.
  • the peptide or polypeptide is an autologous peptide or polypeptide which is native to the target mammal
  • the polypeptide used is preferably rabbit uteroglobin or a fragment thereof, which has been rendered immunogenic for example by coupling to a carrier
  • Peptides or polypeptides which produce an immune response, such as an antibody response, which cross-reacts with uteroglobin may also be useful for diagnostic purposes
  • Antibodies raised against such peptides or polypeptides may be used to detect the presence of uteroglobin in samples Alternatively, the antibodies may be used in passive immunisation methods Techniques for using such antibodies in detection and diagnosis are well known They may include ELISA techniques, or the use of labelled antibodies or anti-antibodies, for example gold labelled antibodies Both competitive and direct assays may be formulated in a conventional manner
  • the invention also provides a peptide or polypeptide which comprises uteroglobin fragment, a peptide or polypeptide derived from uteroglobin, or a variant or peptide mimetic of any of these, which is coupled to a carrier protein and which is able to produce an immune response in a mammal in which antibodies which react with uteroglobin are produced Antibodies produced in this way and their use in diagnosis and as contraceptives in their own right form further aspects of the invention
  • Suitable fragments of uteroglobin are those which constitute a potential epitope These may be small fragments for example of from 4 to 25, suitably from 8 to 17 amino acids in length Indeed, small fragments are preferred as they may be easier to synthesise using chemical means and therefore they may be supplied in greater quantities at reduced cost
  • the risk of unwanted cross-species challenge associated with release of oral vaccine in the field may be avoidable, since small peptides can utilise species-specific motifs in protein sequences Therefore, preferably the fragments are selected so that they are largely species specific and in particular do not cross- react with other species found in similar environments such as the hare
  • variable means that the peptide or polypeptide has a sequence which is similar to that of uteroglobin or fragments thereof, but wherein one or more amino acid residues are different.
  • the changes do not alter function of the peptide or polypeptide in terms of its ability to produce an immune response in a female mammal which affects the fertility of that mammal, although the extent of that response and the resultant affect may be at a different level.
  • peptides or polypeptides which are 60% homologous to the native sequence, suitably more than 80% homologous and preferably more than 90% homologous to the native sequence and which have similar gross biological properties would constitute "variants".
  • peptide mimetic refers to peptides or polypeptides which are designed such that they "mimic” the function of the native uteroglobin or fragment. It is well known that in certain cases, replacement of one amino acid with another may not have a significant effect on the activity of the peptide or polypeptide. Therefore, peptides and polypeptides may be produced which are based upon the sequences of the invention but which do not resemble the sequence of the native uteroglobin protein. However, antibodies raised against such a peptide or polypeptide may be cross-reactive with uteroglobin.
  • the peptide or polypeptide In order to generate a immune response, the peptide or polypeptide should be recognised as "foreign" by the target mammal.
  • a native protein such as uteroglobin or fragments would not be seen as foreign by its natural host.
  • the peptide or polypeptide In order to induce, an immune response, it is necessary for the peptide or polypeptide to be coupled to a carrier protein.
  • a carrier protein include purified protein derivative (PPD), keyhole limpet haemocymin (KLH), bovine serum albumin (BSA) and ovalbumin (OVA).
  • the nature of the carrier has been found to be an important factor in determining the level and duration of the response.
  • the greater molecular size and immunogenicity of the carrier molecule the better the vaccine.
  • KLH is a preferred carrier as compared to OVA.
  • the uteroglobin is rabbit uteroglobin, which has an effect of reducing rabbit fertility.
  • a particularly preferred embodiment of the invention comprises a peptide or polypeptide which comprises rabbit uteroglobin or a fragment thereof coupled to a carrier protein.
  • the polypeptide comprises full-length rabbit uteroglobin coupled to a carrier protein.
  • one or more fragments of rabbit uteroglobin are employed.
  • the skilled person would be able to test using routine methods, for example as illustrated hereinafter, whether any particular fragment (or combination of fragments), variants or peptide mimetics of uteroglobin have the desired activity in the target species.
  • a useful indicator as to potential contraceptive activity would be whether the antiserum produced as a result of innoculation with the selected peptide or polypeptide cross-reacts with uteroglobin. Selection of suitable delivery techniques and formulations to ensure optimum contraceptive effect can also be determined using conventional techniques for fertility assessment, for example as illustrated hereinafter.
  • peptides derived from the third helix of rabbit uteroglobin have the desired biological activity.
  • One such peptide comprises a nonapeptide of sequence:
  • immunogenic peptides are derived from one or more of the three interhelical loops.
  • a particular example of such a peptide, which is based upon all three loops, is a peptide of sequence:
  • Peptides or polypeptides of the invention may be produced by conventional methods For example, they may be synthesised chemically using known techniques. Automated peptide synthesisers are commonly employed. These may be particularly suitable for short peptides as they can be produced quickly and easily in high quantities.
  • Longer polypeptides such as the protein uteroglobin itself may be obtained by purification from natural sources. Modification of the protein thus obtained may then be effected chemically in order to obtain shorter or modified fragments.
  • nucleic acids which encode the desired peptides or polypeptides are prepared, for example by isolation and cloning from natural sources, which may include amplification, or by production ab initio using known nucleic acid synthesising techniques such as automated nucleic acid synthesisers.
  • the nucleic acid is then introduced into an appropriate replication vector or plasmid together with suitable control sequences, such as promoters, enhancers, selection markers etc. as is conventional in the art.
  • the replication vector or plasmid is then introduced into a host cell which may be a eukaryotic or prokarytic cell such as E. coli.
  • Transformed host cells are then selected and cultured and the desired peptide or polypeptide isolated from the resultant culture.
  • Novel nucleic acid sequences, replication vectors or plasmids, transformed cells and processes for preparing the peptides or polypeptides form further aspects of the invention.
  • the peptides or polypeptides are suitably administered in the form of a pharmaceutical composition which further comprises a pharmaceutically acceptable carrier.
  • the carriers may be solid or liquid carriers as is conventional in the art. Liquid carriers include water, saline and aqueous alcohol.
  • the composition may contain additional agents such as adjuvants which potentiates the immune response.
  • adjuvants include Freund's complete and incomplete adjuvant, aluminium compounds such as phosphate and hydroxide, mineral oils such as squalene or biodegradable peanut oil, or mura yl dipeptide which may be incorporated into the mineral oil.
  • Dosages can be determined by the skilled person and will depend upon the nature of the target animal, the particular antigen used, the mode of application etc. For example, initial doses may be divided between several sites in the animal and the number of subsequent administrations for example by injection required varies depending upon the level of response produced by the antigen. However, in general, a dosage range of lOO ⁇ g to lmg/Kg would be acceptable.
  • suitable dosages of UG-PPD administered by injection has been found to be 200 ⁇ g/animal for the initial dose, with subsequent doses of lOO ⁇ g/animal.
  • dosages of the complex with PPD were suitably 500 ⁇ g/animal for the initial dose, with subsequent doses of 250 ⁇ g/animal.
  • a live vector for example an attenuated virus, such as an attenuated vaccina virus, is transformed such that it expresses the antigenic peptide or polypeptide-carrier conjugate.
  • immunocontraceptive compositions of the invention are adapted for oral administration
  • Such compositions will suitably be in the form of biodegradable microspheres as are known in the art (see for example Challacombe S J et al (1992) Immunology 76 164- 168) or liposomes (see for example Walker R I et al , Vaccine (1994) 12 387-400) and immuno stimulatory complexes or "ISCOMS" (see for example Morein B and Akerblom L (1992) in Recombinant DNA Vaccines ed Issacson R L pp369-386 Marcel Dekker New York)
  • Such formulations may be incorporated into bait or food made available for feral populations
  • peptides or polypeptides of the invention may be administered either alone or in combination with other antigens or contraceptive reagents, for example, immunocontraceptives which target sperm anitgens
  • Figure 1 is a computer derived image of rabbit UG, showing the so-called “antiflammin” peptide segment (cross hatched) and the loop peptide segments (arrows) on which peptides of the Examples are based.
  • Figure 2 is a graph showing the results of an ELISA assay of antiserum to peptide L, the composite loop peptide; the upper graph shows antiserum tested against the peptide, and the lower graph shows antiserum tested against native uteroglobin,
  • Figure 3 is a graph showing the results of an ELISA assay of antiserum to peptide F, the antiflammin peptide, the upper graph shows antiserum tested against the peptide, and the lower graph shows antiserum tested against native uteroglobin
  • Figure 4 is a graph showing the results of an ELISA assay of antisera of individual loop peptides 1 , 2, and 3 tested against peptide (left hand column), and antisera tested against native uteroglobin (right hand column);
  • Figure 5a shows the average litter sizes in groups of rabbits immunised with a variety of antigens and an irrelevant control peptide and Figure 5b shows the incidence of resorptions recorded in the experimental groups;
  • Figure 6 shows the time course of primary response to a peptide of the invention inco ⁇ orated in biogradable microparticles
  • Figure 7 shows the response to the same peptide formulations after a booster
  • Figure 8 shows the mean antibody responses of groups of 16 rabbits to a peptide of the invention in various formulations.
  • Isolation techniques such as that described in Example 1 produced relatively small yields of protein.
  • the vector pDS-UG7 which induces high level expression of recombinant rabbit uteroglobin in bacteria (W. Peter et al., Protein Engineering (1989) 3: 61-66) was obtained The expressed recombinant UG (rUG&) forms stable dimers and binds progesterone indistinguishably from native UG.
  • E. coli strain W3110 was transformed with pDS-UG7 and protein expression induced with isopropylthiogalactoside (IPTG). Bacteria were centrifuged, suspended in water and extracted by ultrasonic disruption.
  • IPTG isopropylthiogalactoside
  • Protease inhibitors were added (PMSF, ImM; EDTA, 3mM; benzamidine, ImM; leupeptin, 5mg/ml; Aprotinin l%v/v)
  • the protein extract was gel filtered on a Bio-Gel Al .5m column in PBS containing 0.1% sodium azide and lOmM DTE, and fractions containing rUG7 identified by gel analysis.
  • Peptide L a peptide based on the three inter-helical loops of UG, Leu-15 to Ser-19, Lys-26 to Thr-33, and Ser-47 to Gln-50, synthesises as a single 17-mer peptide of sequence: LGTPSKEFEPDDTSLPQ (SEQ ID NO 2)
  • Loop 2- KEFEPDDT (SEQ ID NO 4)
  • Peptide F a nonapeptide Met-39 to Ser-47 which forms the major part of the third helix of UG and has sequence similarity to the antiflammins (L. Miele et al., Nature
  • Peptides were conjugated to PPD using sulphosuccinimidyl 4-(N- maleimidmethyl)cyclohexane-l-carboxylate (Sulpho-SMCC, Pierce Chemical Co.) as linker.
  • PPD was reacted with linker at pH7.5 for 30 minutes, the pH adjusted to pH 6.0 and activated PPD separated by gel filtration from uncoupled linker.
  • Peptides of Examples 1, 2 and 3 were coupled overnight to activated PPD under nitrogen at pH 7.0. Uncoupled peptide molecules were removed by dialysis.
  • Immunisation of BCG-primed rabbits using the peptide or protein conjugates from Example 4 was carried out with a minimum of two injections. Primary injections of antigen peptide-PPD were given in incomplete Freund's adjuvant both intramuscularly and subcutaneously and subsequent booster injections were given subcutaneously with a 3 week interval between injections.
  • Group 1 A control peptide with no relationship to the reproductive system
  • Group 2 Peptide F coupled to KLH (F-KLH); and
  • Group 3 UG coupled to KLH (UG-KLH).
  • a serum was raised by immunisation of a sheep with UG-KLH, in Freund's adjuvant
  • the course consisted of three multi-site injections at 4-week intervals
  • the serum IgG antibody fraction was purified by protein G affinity chromatography (ProSep G column); normal IgG from a nonimmunised sheep was prepared in similar fashion as the control
  • test group received 4 subcutaneous injections, each of 7.5mg sheep anti-UG IgG, 2 days before and at 4, 11, and 18 days after mating, the control group received 4 injections of normal sheep IgG to the same amount Animals were autopsied on day 25 of pregnancy
  • Example 7 Since both the trials of Example 7 and Example 8 compared the effect of UG antibodies versus controls, the results can be combined as shown in Table V
  • Conjugates as prepared in Example 4 above were incorporated into microparticles by mixing a 15mg/ml conjugate aqueous solution (2ml) with 10ml of 6%w/v solution of poly(DL lactide co-glycolide) with a lactide glycolide ratio of either 50 50 or 75 25 to produce a water-in-oil emulsion
  • This primary emulsion was mixed with polyvinyl alcohol (PVA) stabiliser to produce a water-in-oil-in- water suspension which was stirred overnight to remove solvent
  • PVA polyvinyl alcohol
  • Particle size range was determined using a BCA assay followed by disruption of approximately 5mg particles in 2ml of 5% w/v sodium dodecyl sulphate in 0 1M sodium hydroxide overnight Calibration curves were constructed from a series dilution of the respective conjugate Microparticles were stored freeze dried below 5°C with dessicant
  • Antibody responses to peptide L after immunisation in biodegradable microparticles In order to design a vaccine which could be used for oral delivery to rabbits in the wild, antibody responses were induced to peptide L incorporated into biodegradable polylactide- coglycolide (PLGA) microparticles. These have been shown to be effective carriers for oral immunisation in rodents UG loop peptide complexed to KLH (L-KLH) or OVA (L-OVA) was incorporated into microparticles (lactide:glycolide ration 75 25) and administered to rabbits by parenteral routes in order to assess efficacy
  • PLGA biodegradable polylactide- coglycolide
  • Example 2 Using the methodology of Example 1 1, four groups of 16 rabbits each received L-KLH in a different formulation as follows:
  • Group 1 L-KLH in complete Freund's adjuvant
  • Group 3 L-KLH in 50:50 lactide:glycolide microparticles; and Group 4: L-KLH in 75:25 lactide:glycolide microparticles.
  • microparticle formulations administered to Groups 3 and 4 provide different rates of antigen release (fast and slow respectively).

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Abstract

La présente invention concerne la production d'anti-sérums dirigés contre des petites peptides ou polypeptides qui réagissent de manière croisée avec l'utéroglobine, permettant un diagnostic et une détection ainsi que la mise en oeuvre de méthodes immunocontra ceptives. En particulier, l'invention se rapporte à une méthode pour réguler la fertilité d'un mammifère femelle, spécialement un mammifère sauvage, tel le lapin de garenne. Cette méthode consiste à administrer à un mammifère un peptide ou polypeptide qui st imule une réponse immunitaire, ladite réponse incluant la production d'éléments qui fixent l'utéroglobine et réduisent la fertilité de ladite femelle de mammifère. Les peptides ou polypeptides utilisables avec la méthode sont des peptides ou polypeptides comprenant (a) l'utéroglobine ou un fragment de celle-ci, un peptide ou polypeptide dérivé de l'utéroglobine ou une variante ou une peptide mimétique de ceux-ci (b) une protéine de transport. Ils peuvent être appliqués dans une formulation classique de vaccin, incluant l'usage des vecteurs viraux de vaccin. De manière préférentielle, on les formule dans des compositions convenant à l'administration orale. De nouveaux peptides ou polypeptides utilisables avec la méthode, leur production ainsi que d'autres aspects sont aussi décrits et revendiqués.
PCT/GB1997/001740 1996-06-29 1997-06-26 Methodes immunocontraceptives et peptide ou polypeptides a utiliser dans lesdites methodes WO1998000536A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU33500/97A AU3350097A (en) 1996-06-29 1997-06-26 Immunocontraceptive methods and peptide or polypeptides for use in these methods
CA002259237A CA2259237A1 (fr) 1996-06-29 1997-06-26 Methodes immunocontraceptives et peptides ou polypeptides utilises dans cette methode

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GBGB9613705.4A GB9613705D0 (en) 1996-06-29 1996-06-29 Novel peptides
GB9613705.4 1996-06-29

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001040288A1 (fr) * 1999-11-30 2001-06-07 Bioroad Gene Development Ltd. Shanghai Nouveau polypeptide, uteroglobine humaine 13, et polynucleotide codant pour ce polypeptide
WO2009033717A3 (fr) * 2007-09-11 2009-06-11 Mondobiotech Lab Ag Utilisation d'un peptide comme agent thérapeutique

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989005147A1 (fr) * 1987-11-19 1989-06-15 The United States Of America, As Represented By Th Nouveaux agents anti-inflammatoires

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989005147A1 (fr) * 1987-11-19 1989-06-15 The United States Of America, As Represented By Th Nouveaux agents anti-inflammatoires

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
A K ABBAS ET AL.: "cellular and molecular immunology", 1994, W B SAUNDERS, PHILADELPHIA, PA, USA, XP002044069 *
CHEMICAL ABSTRACTS, vol. 117, no. 7, 17 August 1992, Columbus, Ohio, US; abstract no. 65032, XP002044070 *
D P STITES & A I TERR: "Basic and clinical immunology", 1991, PRENTICE-HALL INT., EAST NORWALK, CONN., USA, XP002044066 *
I M ROITT & P J DELVES: "Encyclopedia of Immunology", 1992, HARCOURT BRACE JOVANOVITCH, LONDON, XP002044067, 194140 *
I M ROITT: "Essential immunology", 1988, BLACKWELL SCIENTIFIC PUBLICATIONS, OXFORD, XP002044068, 154670 *
L MIELE ET AL.: "Novel anti-inflammatory peptides from the region of highest similarity between uteroglobin and lipocortin I", NATURE., vol. 335, 20 October 1988 (1988-10-20), LONDON GB, pages 726 - 730, XP002044065 *
S MAMMI ET AL.: "Conformation of uteroglobin fragments", BIOPOLYMERS, vol. 32, no. 4, 1992, pages 341 - 346 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001040288A1 (fr) * 1999-11-30 2001-06-07 Bioroad Gene Development Ltd. Shanghai Nouveau polypeptide, uteroglobine humaine 13, et polynucleotide codant pour ce polypeptide
WO2009033717A3 (fr) * 2007-09-11 2009-06-11 Mondobiotech Lab Ag Utilisation d'un peptide comme agent thérapeutique
US8349805B2 (en) 2007-09-11 2013-01-08 Mondobiotech Laboratories Ag Use of Gonadorelin as a therapeutic agent

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CA2259237A1 (fr) 1998-01-08
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