WO2024052563A4 - Myeloid-derived growth factor for use in treating cardiogenic shock - Google Patents

Myeloid-derived growth factor for use in treating cardiogenic shock Download PDF

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Publication number
WO2024052563A4
WO2024052563A4 PCT/EP2023/074803 EP2023074803W WO2024052563A4 WO 2024052563 A4 WO2024052563 A4 WO 2024052563A4 EP 2023074803 W EP2023074803 W EP 2023074803W WO 2024052563 A4 WO2024052563 A4 WO 2024052563A4
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WO
WIPO (PCT)
Prior art keywords
seq
variant
mydgf
fragment
amino acid
Prior art date
Application number
PCT/EP2023/074803
Other languages
French (fr)
Other versions
WO2024052563A1 (en
Inventor
Kai Christoph Wollert
Yong Wang
Original Assignee
Boehringer Ingelheim International Gmbh
Medizinische Hochschule Hannover
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 Boehringer Ingelheim International Gmbh, Medizinische Hochschule Hannover filed Critical Boehringer Ingelheim International Gmbh
Publication of WO2024052563A1 publication Critical patent/WO2024052563A1/en
Publication of WO2024052563A4 publication Critical patent/WO2024052563A4/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027New or modified breeds of vertebrates
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027New or modified breeds of vertebrates
    • A01K67/0275Genetically modified vertebrates, e.g. transgenic
    • A01K67/0276Knock-out vertebrates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/02Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00Modified animals
    • A01K2207/30Animals modified by surgical methods
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00Modified animals
    • A01K2207/35Animals modified by environmental factors, e.g. temperature, O2
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/07Animals genetically altered by homologous recombination
    • A01K2217/075Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00Animals characterised by species
    • A01K2227/10Mammal
    • A01K2227/105Murine
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00Animals characterised by purpose
    • A01K2267/03Animal model, e.g. for test or diseases
    • A01K2267/035Animal model for multifactorial diseases
    • A01K2267/0375Animal model for cardiovascular diseases

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Environmental Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Cardiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Zoology (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Hospice & Palliative Care (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biotechnology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

The present invention relates to the protein myeloid-derived growth factor (MYDGF) or nucleic acids encoding said protein for use in treating and/or preventing cardiogenic shock. The present invention also relates to vectors comprising the nucleic acid, host cells expressing the nucleic acid, pharmaceutical compositions comprising said protein, nucleic acid, vector or host cell for use in treating and/or preventing cardiogenic shock, and to methods for treating and/or preventing cardiogenic shock. The present invention further relates to a method of preparing an animal model of cardiogenic shock, and to animals obtained by said method.

Claims

AMENDED CLAIMS received by the International Bureau on 07 March 2024 (07.03.2024)
1. Myeloid-derived growth factor (MYDGF) protein comprising SEQ ID NO: 1 or SEQ ID NO: 3, or a fragment or a variant thereof, wherein the protein or the fragment or the variant thereof exhibits the biological function of MYDGF, wherein the variant comprises an amino acid sequence with at least 85% amino acid sequence identity to SEQ ID NO: 1 or SEQ ID NO: 3, for use in treating and/or preventing cardiogenic shock.
2. The MYDGF for use according to claim 1, wherein the MYDGF comprises:
(i) SEQ ID NO: 1; or
(ii) a fragment or variant of SEQ ID NO: 1 exhibiting the biological function of MYDGF, wherein the variant comprises an amino acid sequence with at least 85% amino acid sequence identity to SEQ ID NO: 1.
3. The MYDGF for use according to claim 1, wherein the MYDGF protein consists of SEQ ID NO: 1, of SEQ ID NO: 3, or of a variant of SEQ ID NO: 3 having 99% sequence identity to SEQ ID NO: 3.
4. A nucleic acid encoding MYDGF protein comprising SEQ ID NO: 1 or SEQ ID NO: 3, or a fragment or a variant thereof, wherein the protein or the fragment or the variant thereof exhibits the biological function of MYDGF, wherein the variant comprises an amino acid sequence with at least 85% amino acid sequence identity to SEQ ID NO: 1 or SEQ ID NO: 3, for use in treating and/or preventing cardiogenic shock.
5. The nucleic acid for use according to claim 4, wherein the nucleic acid encodes an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 1.
6. A vector comprising the nucleic acid of claim 4 or 5, for use in treating and/or preventing cardiogenic shock.
7. A host cell comprising the vector according to claim 6 and expressing the nucleic acid, for use in treating and/or preventing cardiogenic shock.
41
AMENDED SHEET (ARTICLE 19)
8. A pharmaceutical composition comprising the MYDGF protein or a fragment or a variant thereof according to any one of claims 1 to 3, the nucleic acid according to any one of claims 4 or 5, the vector according to claim 6, or the host cell according to claim 7 for use in treating and/or preventing cardiogenic shock.
9. The pharmaceutical composition for use according to claim 8, wherein said pharmaceutical composition is administered through the oral, intravenous, subcutaneous, intramucosal, intraarterial, intramuscular or intracoronary route.
10. The pharmaceutical composition for use of claim 9, wherein the administration is through one or more bolus injection(s) and/or infusion(s).
11. A method of treating and/or preventing cardiogenic shock, comprising administering to a patient in need thereof a therapeutically effective amount of MYDGF protein comprising SEQ ID NO: 1 or SEQ ID NO: 3, or fragment or variant thereof, wherein the protein or the fragment or the variant thereof exhibits the biological function of MYDGF, wherein the variant comprises an amino acid sequence with at least 85% amino acid sequence identity to SEQ ID NO: 1 or SEQ ID NO: 3.
12. A method of treating and/or preventing cardiogenic shock comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising myeloid-derived growth factor (MYDGF) protein comprising SEQ ID NO: 1 or SEQ ID NO: 3, or a fragment or a variant thereof, wherein the protein or the fragment or the variant thereof exhibits the biological function of MYDGF, wherein the variant comprises an amino acid sequence with at least 85% amino acid sequence identity to SEQ ID NO: 1 or SEQ ID NO: 3.
13. The method according to claim 11 or 12, wherein the MYDGF comprises:
(i) SEQ ID NO: 1; or
(ii) wherein the fragment or variant is a fragment or variant of SEQ ID NO: 1 and exhibits the biological function of MYDGF, wherein the variant comprises an amino acid sequence with at least 85% amino acid sequence identity to SEQ ID NO: 1.
14. The method according to any one of claims 11 to 13, wherein the MYDGF or fragment or variant thereof is administered through one or more bolus injection(s) and/or infusion(s), preferably in a pharmaceutically accepted carrier and/or excipient.
42
AMENDED SHEET (ARTICLE 19)
15. A method for producing a non-human mammalian model of cardiogenic shock, the method comprising:
(i) transiently ligating a coronary artery of the mammal, (ii) establishing reperfusion, and
(iii) ventilating the mammal with a fraction of inhaled oxygen of about 0.18 or less.
16. The method of claim 15, wherein the non-human mammal is a rodent, preferably wherein the non-human mammal is a mouse.
17. The method of claim 15 or 16, wherein the coronary artery is ligated for about 30 minutes to about 90 minutes before reperfusion is established.
18. The method according to any one of claims 15 to 17, wherein the mammal is ventilated with a fraction of inhaled oxygen of about 0.16.
43
AMENDED SHEET (ARTICLE 19)
PCT/EP2023/074803 2022-09-08 2023-09-08 Myeloid-derived growth factor for use in treating cardiogenic shock WO2024052563A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263374942P 2022-09-08 2022-09-08
US63/374,942 2022-09-08

Publications (2)

Publication Number Publication Date
WO2024052563A1 WO2024052563A1 (en) 2024-03-14
WO2024052563A4 true WO2024052563A4 (en) 2024-04-25

Family

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Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/EP2023/074803 WO2024052563A1 (en) 2022-09-08 2023-09-08 Myeloid-derived growth factor for use in treating cardiogenic shock
PCT/EP2023/074804 WO2024052564A1 (en) 2022-09-08 2023-09-08 Myeloid-derived growth factor for use in treating cardiogenic shock

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/EP2023/074804 WO2024052564A1 (en) 2022-09-08 2023-09-08 Myeloid-derived growth factor for use in treating cardiogenic shock

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Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3584341D1 (en) 1984-08-24 1991-11-14 Upjohn Co RECOMBINANT DNA COMPOUNDS AND EXPRESSION OF POLYPEPTIDES LIKE TPA.
CA2257137A1 (en) 1996-06-11 1997-12-18 Merck & Co., Inc. Synthetic hepatitis c genes
WO2004069173A2 (en) 2003-01-31 2004-08-19 The Trustees Of The University Of Pennsylvania Methods for modulating an inflammatory response
US20080004232A1 (en) 2006-05-09 2008-01-03 John Wilkins Characterization of c19orf10, a Novel Synovial Protein
EP2130547A1 (en) 2008-06-06 2009-12-09 Giuliani International Limited IL-25 for use in the treatment of inflammatory diseases
CN110922467A (en) 2013-01-17 2020-03-27 汉诺威医学院 Factor 1 protein, factor 2 protein and inhibitors thereof for treating or preventing diseases
WO2021148411A1 (en) 2020-01-21 2021-07-29 Boehringer Ingelheim International Gmbh Myeloid-derived growth factor for use in treating or preventing fibrosis, hypertrophy or heart failure
EP4121583A1 (en) * 2020-03-20 2023-01-25 Yale University Rapid extracellular antibody profiling (reap) for the discovery and use of said antibodies
CN114470163A (en) * 2022-02-08 2022-05-13 西安交通大学医学院第一附属医院 Application of recombinant human medullary growth factor in treating renal ischemia reperfusion injury

Also Published As

Publication number Publication date
WO2024052564A1 (en) 2024-03-14
WO2024052563A1 (en) 2024-03-14

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