GENERATION OF BRAIN AND SPINAL CORD NEURONS, CARDIAC MYOCYTES, RENAL NEPHRONS AND HEPATOCYTES USING REG PEPTIDES, PEPTIDOMIMETICS, SMALL MOLECULES AND STIMULATORY ANTIBODIES TO REG RECEPTOR

• US 20190330289A1
• Filed: 07/15/2019
• Published: 10/31/2019
• Est. Priority Date: 10/26/2012
• Status: Abandoned Application

• Current Assignee: Claresa Levetan
• Original Assignee: Claresa Levetan
• Inventors: Levetan, Claresa
• Application Number:
  US16/511,718
• Publication Number:
  US 20190330289A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/22 Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61K 35/34 Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes vascular smooth muscle A61K35/44
• CPC Class Codes: A61K 35/407 Liver; Hepatocytes
• CPC Class Codes: A61K 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61K 35/51 Umbilical cord; Umbilical cord blood; Umbilical stem cells
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/474 Pancreatic thread protein; Reg protein
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2839 against the integrin superfamily
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/75 : Agonist effect on antigen

Abstract

Peptides that are bioactive regions and optimized bioactive regions of the human and mammalian Reg gene proteins and that are capable of generation of tissues such as brain, spinal cord, heart, liver, and kidney are described. In particular, 7-15-amino acid Reg peptides and optimized Reg peptides are disclosed which are capable of in vivo and ex vivo transformation of progenitor cells, progenitor tissue and stem cells into specialized cells and tissues, including functioning brain and spinal cord neurons, cardiac myocytes, liver hepatocytes and renal nephrons. Methods of in vivo and ex vivo transformation of progenitor cells into differentiated cells and tissues are also described.

Claims

1. An isolated or modified peptide having an amino acid sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

5, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, SEQ ID NO;

11, SEQ ID NO;

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, SEQ ID NO;

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

21, SEQ ID NO;

22, SEQ ID NO;

23, SEQ ID NO;

24, SEQ ID NO;

25, SEQ ID NO;

26, and SEQ ID NO;

27.

2. A pharmaceutical formulation comprising the peptide of claim 1.

3. The pharmaceutical formulation of claim 2, wherein the formulation is a soluble liposome or nanoparticle preparation.

4. The pharmaceutical formulation of claim 2, wherein the formulation comprises a targeting agent for targeted administration to heart, brain, spinal column, liver, or kidney.

5. A method of treating a subject in need of one or more differentiated cells or tissue types, comprising administering to the subject a peptide having Reg Receptor binding activity, wherein the amount of peptide is effective for forming differentiated cells or tissues from progenitor cells in the subject in vivo.

6. The method of claim 5, wherein the peptide having Reg Receptor binding activity has an amino acid sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

5, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, SEQ ID NO;

11, SEQ ID NO;

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, SEQ ID NO;

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

21, SEQ ID NO;

22, SEQ ID NO;

23, SEQ ID NO;

24, SEQ ID NO;

25, SEQ ID NO;

26, and SEQ ID NO;

27.

7. The method of claim 5, wherein the one or more differentiated cells or tissue types are heart, liver, brain, spinal column, or kidney cells or tissues.

8. The method of claim 5, wherein the peptide is administered directly to the heart, liver, brain, spinal cord or kidney of a subject.

9. The method of claim 5, wherein the peptide is administered by way of intravenous, subcutaneous, intra-arterial, or intrathecal delivery.

10. The method of claim 5, wherein the subject has a condition selected from the group consisting of heart disease, myocardial infarction, stroke, acute brain injury, neurodegenerative disease, spinal cord injury, peripheral neuropathy, acute and chronic kidney disease and liver disease.

11. A method of treating a subject in need of one more differentiated cells or tissues, the method comprising:

culturing a plurality of progenitor cells ex vivo;

contacting the progenitor cells with a peptide having Reg Receptor binding activity, wherein the amount of peptide is effective for transforming the progenitor cells to differentiated cells or tissues in culture; and

administering the one or more differentiated cells or tissues to the subject.

12. The method of claim 11, wherein the peptide having Reg Receptor binding activity has an amino acid sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

5, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, SEQ ID NO;

11, SEQ ID NO;

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, SEQ ID NO;

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

21, SEQ ID NO;

22, SEQ ID NO;

23, SEQ ID NO;

24, SEQ ID NO;

25, SEQ ID NO;

26, and SEQ ID NO;

27.

13. The method of claim 11, wherein the progenitor cells are selected from the group consisting of neural stems cells, tissue stem cells, mesenchymal stem cells, totipotent embyronic stem cells, multipotent stem cells, pluripotent stem cells, including embryonic cells, adult somatic stem cells, human adult bone-marrow derived stem cells, umbilical cord stems cells, human amniotic membrane-derived mesenchymal cells, mammalian stem cells, cord cells, and ectodermal stem cells.

14. The method of claim 11, wherein the differentiated cells or tissues are selected from the group consisting of brain, spinal cord, heart, kidney and liver cells or tissues.

15. The method of claim 11, wherein the differentiated cells or tissues are administered directly to the heart, liver, brain, spinal cord or kidney of a subject.

16. The method of claim 11, wherein the subject has a condition selected from the group consisting of heart disease, myocardial infarction, stroke, acute brain injury, neurodegenerative disease, spinal cord injury, peripheral neuropathy, acute and chronic kidney disease and liver disease.