WO2013014269A1 - Procédé pour la promotion de la croissance d'un animal nouveau-né - Google Patents

Procédé pour la promotion de la croissance d'un animal nouveau-né Download PDF

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Publication number
WO2013014269A1
WO2013014269A1 PCT/EP2012/064773 EP2012064773W WO2013014269A1 WO 2013014269 A1 WO2013014269 A1 WO 2013014269A1 EP 2012064773 W EP2012064773 W EP 2012064773W WO 2013014269 A1 WO2013014269 A1 WO 2013014269A1
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WO
WIPO (PCT)
Prior art keywords
pyy
animal
antibodies
newborn
composition
Prior art date
Application number
PCT/EP2012/064773
Other languages
English (en)
Inventor
Holger Lehmann
Marc-Antoine Driancourt
Original Assignee
Intervet International B.V.
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 Intervet International B.V. filed Critical Intervet International B.V.
Publication of WO2013014269A1 publication Critical patent/WO2013014269A1/fr

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Classifications

    • 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
    • C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • 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
    • A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies

Definitions

  • the present invention pertains to a method to promote growth of a newborn animal, i.e. any method to stimulate the growth of an animal versus a control animal (not subjected to the method), for example by increasing food efficiency or growth speed.
  • a control animal not subjected to the method
  • the growth of a newborn animal, in particular a vertebrate can be promoted by administering anti-PYY antibodies to the newborn animal.
  • PYY (also known as Peptide YY or Peptide tyrosine-tyrosine) is a member of the pancreatic polypeptide family that also includes neuropeptide Y (NPY), and is produced by endocrine cells (called L cells) of the lower intestine and the pancreas of vertebrates (Karra et al. in: Molecular and Cellular Enodcrinology ⁇ S, 2010, 120-128), including mammals, poultry and fish.
  • NPY neuropeptide Y
  • L cells endocrine cells
  • PYY is a peptide that in most animals contains 36 amino acids, although in chickens it is 37 amino acids long, displaying alanine (-1 position) before the first tyrosine (Conlon et al. in: FEBS letters, 313: 225-228).
  • PYY Two main forms of PYY have been described, viz. the full-length PYY1 -36 and a truncated form PYY3-36, each form is denoted as "PYY" in the art.
  • the said truncated form is a 34 amino acid form produced by cleavage of the N-terminal Tyr-Pro residue (or Ala-Tyr-Pro in the case of chicken PYY) from PYY1-36 by the enzyme dipeptidyl-peptidase IV.
  • PYY3-36 is the main circulating form of the peptide (although it is not excluded that other truncated forms, e.g. a form defining the portion that binds to the PYY receptor, may exist or can be artificially provided).
  • PYY has a range of biological effects (see the Karra et al. reference indicated here- above). Circulating PYY levels increase in response to nutrient ingestion. Caloric load, food consistency and nutrient composition all affect PYY concentrations. It has also been shown that circulating postprandial PYY levels correlate with postprandial energy expenditure and the thermic effect of food. A positive correlation between postprandial PYY concentrations and subjective satiety has been reported. Peripheral administration of PYY3-36 reduced food intake in rodents and normal weight humans, while, on the opposite, transgenic mice that lacked Pyy were hyperphagic when freely feeding and ate significantly more than their wild-type littermates. These PyyKO mice had increased subcutaneous and visceral adiposity. In other words, they had become obese.
  • decreasing the level of circulating PYY in newborn animals may also stimulate food intake in these particular animals, and if so, may promote the same processes in these animals that would induce obesity in an adult animal, which promotion on it's turn might lead to additional growth in these newborn animals instead of obesity, that is if the metabolism of these newborn animals is such that they are programmed to grow instead of becoming obese.
  • the invention also pertains to the use of PYY to raise anti-PYY antibodies for the manufacture of a composition comprising these antibodies that after administration to a newborn animal promote growth of this animal. Also, the invention pertains to the use of PYY to manufacture a composition comprising immunogenic PYY for administration to a female animal to induce anti-PYY antibodies in the said animal for passing these antibodies to a newborn animal by allowing the newborn animal to drink milk from the female animal.
  • a newborn animal is an animal right after birth, i.e. right after exposure to the exterior environment, until it reaches about 10% of its adult weight, in particular about 5% of its adult weight.
  • the moment of birth is defined as the moment when the animal leaves its egg.
  • Obesity is the presence of excess body fat, particularly present under the skin and around internal organs, as a result of an uneven increase in adipose tissue with respect to other tissue such as bone and muscle.
  • the antibodies are administered during the first 4 weeks after birth of the animal.
  • the newborn animals are very susceptible for passive immunisation, in particular when the antibodies are administered during the first week after birth of the animal, preferably even during the first day after birth of the animal.
  • the immune system of newborn animals may explain why early immunisation with antibodies is very effective.
  • the antibodies are administered orally.
  • Oral administration of antibodies may be convenient and safe.
  • the gut allows almost free passing of antibodies into the circulatory system.
  • the antibodies are administered through suckling of milk from a lactating animal that has circulating anti-PYY antibodies. This method has shown to be very convenient and effective for application of the present invention. Indeed, colostrum (the milk produced during the first 24-48 hours after giving birth) is known to comprise a high concentration of antibodies.
  • the anti-PYY antibodies in the lactating animal are induced via administration of a composition comprising immunogenic PYY (i.e. PYY in a form such that the immune system of a subject animal may raise anti-bodies directed against PYY upon administration of the composition to the animal).
  • the composition comprising the immunogenic PYY is administered to a female animal before it is lactating. As soon as the animal is lactating, one or more newborn animals are allowed to drink milk from the said female animal, for example by simply laying the one or more animals to the female animal, or by leaving the one or more animals to the female animal when she has given birth to the one or more newborn animals.
  • this embodiment has shown to be very effective in raising antibodies.
  • healthy animals such as humans and rats already have autoantibodies against PYY in the circulatory system (Fetissov et al. in: Nutrition 24, 2008, 854-859)
  • the lactating animal has received the immunogenic composition during pregnancy, preferably multiple times.
  • Typical dosage of the immunogenic PYY lies in a range between 50 and 1000 ⁇ g, administered via a volume typically between 0.1 and 5 ml, preferably between 0.2 and 2 ml.
  • the composition comprises PYY 3-36.
  • This truncated form of PYY has proven to be effective as an immunogen to raise antibodies against PYY.
  • the PYY is conjugated to a carrier, such as for example keyhole limpet hemocyanine (KLH).
  • KLH keyhole limpet hemocyanine
  • the newborn animal is a monogastric, in particular a swine.
  • the invention will be explained in more detail based on the following examples.
  • Example 1 describes polypeptide YY.
  • Example 2 describes a study to assess the effect of anti-PYY antibodies in a vertebrate.
  • Example 3 describes an experiment to assess the passing of anti-PYY antibodies via milk of lactating animals to newborn animals.
  • Example 1
  • Sequence identifier 1 shows the amino acid sequence of pig PYY1 -36 (it is noted that other forms of PYY may exist, such as for example PYY3-36, or may be artificially produced taken account of the above described information about the structure of full-length PYY).
  • the amino acid sequence of rat PYY is 100% identical to SEQ ID No 1.
  • Human PYY1-36 (SEQ ID No 2) is slightly different and has an overall identity of 94%.
  • Chicken PYY1 -36 (SEQ ID No 3) has an identity of 69% to pig PYY. This is a clear indication of the high degree of conservation of PYY in vertebrates.
  • PYY at least covers the two known forms of PYY according to SEQ ID No 1 , viz. PYY1 -36 and PYY3-36, and homologs having at least 69% identity with these forms.
  • This example describes a study to asses the effects of anti-PYY antibodies, raised by active immunisation in sows, on the sows themselves and on their progeny.
  • the PYY group was actively immunized with a vaccine containing PYY antigens (called the "PYY vaccine").
  • a first injection (1 ml; i.m.) with the PYY vaccine was given at inclusion, immediately after a positive pregnancy diagnosis (i.e. around day 28 of pregnancy).
  • Three additional (1 ml; i.m.) vaccinations were given 3 weeks apart, with the last one administered around one week before farrowing.
  • Gilts from the placebo group were injected with a placebo vaccine (the same as the PYY vaccine, but no PYY3-36-KLH present) at the same times.
  • Anti-PYY antibody levels changes in body weight and dorsal fat thickness were monitored during pregnancy and lactation.
  • the mother animals of the two groups had similar body weights (both around 205 kg at farrowing and around 180 kg at weaning) and dorsal fat thickness (both around 25 mm at farrowing and around 21 mm at weaning), despite the fact that the PYY group displayed circulating anti-PYY antibodies, whereas the placebo group had not.
  • the vaccine had raised significant levels of PYY antibodies, but the presence of these antibodies had no apparent effect on the body weight and dorsal fat thickness of the pregnant animals.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biophysics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Endocrinology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente invention concerne un procédé de promotion de la croissance d'un animal nouveau-né, le procédé comprenant l'administration d'anticorps anti-PYY à l'animal nouveau-né. L'invention concerne également l'utilisation de PYY pour générer des anticorps anti-PYY pour la fabrication d'une composition comprenant ces anticorps qui, après l'administration à un animal nouveau-né, permettent la croissance de cet animal, et l'utilisation de PYY pour la fabrication d'une composition comprenant un PYY immunogène pour l'administration à un animal femelle pour induire des anticorps anti-PYY chez ledit animal pour transmettre ces anticorps à un animal nouveau-né en permettant à l'animal nouveau-né de boire le lait provenant de l'animal femelle.
PCT/EP2012/064773 2011-07-28 2012-07-27 Procédé pour la promotion de la croissance d'un animal nouveau-né WO2013014269A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161512485P 2011-07-28 2011-07-28
US61/512,485 2011-07-28

Publications (1)

Publication Number Publication Date
WO2013014269A1 true WO2013014269A1 (fr) 2013-01-31

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1224870A1 (fr) * 2001-01-23 2002-07-24 Xeris Utilisation de la tributyrine en alimentation animale et additif alimentaire correspondant
WO2005113600A2 (fr) 2004-05-18 2005-12-01 Haptogen Ltd Methodes de regulation, de traitement et de prise en charge de l'obesite
WO2006108234A1 (fr) * 2005-04-13 2006-10-19 Garvan Institute Of Medical Research Animal modifie depourvu du gene pyy fonctionnel, anticorps monoclonaux fixant les isoformes pyy et leurs utilisations

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1224870A1 (fr) * 2001-01-23 2002-07-24 Xeris Utilisation de la tributyrine en alimentation animale et additif alimentaire correspondant
WO2005113600A2 (fr) 2004-05-18 2005-12-01 Haptogen Ltd Methodes de regulation, de traitement et de prise en charge de l'obesite
WO2006108234A1 (fr) * 2005-04-13 2006-10-19 Garvan Institute Of Medical Research Animal modifie depourvu du gene pyy fonctionnel, anticorps monoclonaux fixant les isoformes pyy et leurs utilisations

Non-Patent Citations (17)

* Cited by examiner, † Cited by third party
Title
BILCHIK, SURGERY, vol. 116, 1994, pages 1153 - 1157
BOEY D ET AL: "Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity.", DIABETOLOGIA JUN 2006 LNKD- PUBMED:16680491, vol. 49, no. 6, June 2006 (2006-06-01), pages 1360 - 1370, XP002685406, ISSN: 0012-186X *
CONLON ET AL., FEBS LETTERS, vol. 313, pages 225 - 228
CROOM ET AL., THE JOURNAL OF APPLIED POULTRY RESEARCH, vol. 8, 1999, pages 242 - 252
FETISSOV ET AL., NUTRITION, vol. 24, 2008, pages 854 - 859
HERMANSON, G.T.: "Bioconjugate Techniques", 1996, ACADEMIC PRESS
KARRA ET AL., MOLECULAR AND CELLULAR ENODCRINOLOGY, vol. 316, 2010, pages 120 - 128
KEIRE, PEPTIDES, vol. 23, 2002, pages 305 - 321
LEONARD R. JOHNSON ET AL.: "Physiology of the Gastrointestinal Tract", vol. 2, 2006, pages: 141
NAGATA E ET AL: "Altered gene expressions of ghrelin, PYY, and CCK in the gastrointestinal tract of the hyperphagic intrauterine growth restriction rat offspring.", HORMONE AND METABOLIC RESEARCH = HORMON- UND STOFFWECHSELFORSCHUNG = HORMONES ET MÉTABOLISME MAR 2011 LNKD- PUBMED:21264794, vol. 43, no. 3, March 2011 (2011-03-01), pages 178 - 182, XP002685248, ISSN: 1439-4286 *
PEDERSEN ET AL., JOURNAL OF PEPTIDE SCIENCE, vol. 15, 2009, pages 753 - 759
POULTRY SCIENCE, vol. 78, 1999, pages 1320 - 1322
RACHEL L BATTERHAM ET AL: "Critical role for peptide YY in protein-mediated satiation and body-weight regulation", CELL METABOLISM, CELL PRESS, UNITED STATES, vol. 4, no. 3, 1 September 2006 (2006-09-01), pages 223 - 233, XP002630773, ISSN: 1550-4131, [retrieved on 20060905], DOI: 10.1016/J.CMET.2006.08.001 *
TANIA SIAHANIDOU ET AL: "Peptide YY (3-36) Represents a High Percentage of Total PYY Immunoreactivity in Preterm and Full-Term Infants and Correlates Independently With Markers of Adiposity and Serum Ghrelin Concentrations", PEDIATRIC RESEARCH, vol. 62, no. 2, 1 August 2007 (2007-08-01), pages 200 - 203, XP055038382, ISSN: 0031-3998, DOI: 10.1203/PDR.0b013e3180a76dad *
THE JOURNAL OF APPLIED POULTRY RESEARCH, vol. 10, 2001, pages 380 - 384
WAEGELE ET AL., BIOCHEMISTRY, vol. 49, 2010, pages 7659 - 7664
WOJCICKI JANET M: "Peptide YY in children: a review.", JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM : JPEM 2012 LNKD- PUBMED:22768648, vol. 25, no. 3-4, 2012, pages 227 - 232, XP008156335, ISSN: 0334-018X *

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