# US 9,518,085 B2 · Compounds and pharmaceutical combinations for the treatment of neurodegenerative and ischemic brain diseases

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,518,085 B2
- Document ID: US9518085B2
- Status: Granted
- Kind: B2
- Application number: 14/127,369
- Filed: 2012-06-29
- Published: 2014-12-04
- Granted: 2016-12-13
- Earliest claimed: 2011-07-01
- Assignees: Centro de Ingenieria Genetica y Biotechnologia
- Applicants: Giselle Penton Rol; Alexey Llopiz Arzuaga; Javier Marin Prida; Eduardo Penton Arias; Efrain Rodriguez Jimenez; Alexis Musacchio Lasa; Vladimir Armando Besada Perez; Gilberto Lazaro Pardo Andreu; Luis Javier Gonzalez Lopez; Nancy Pavon Fuentes; Gerardo Enrique Guillen Nieto; Pedro Antonio Lopez Saura
- Inventors: Giselle Penton Rol; Alexey Llopiz Arzuaga; Javier Marin Prida; Eduardo Penton Arias; Efrain Rodriguez Jimenez; Alexis Musacchio Lasa; Vladimir Armando Besada Perez; Gilberto Lazaro Pardo Andreu; Luis Javier Gonzalez Lopez; Nancy Pavon Fuentes; Gerardo Enrique Guillen Nieto; Pedro Antonio Lopez Saura
- Web page: https://patentgrep.com/patent/US9518085B2

## CPC

- A61K 31/409: having four such rings, e.g. porphine derivatives, bilirubin, biliverdine (hemin, hematin A61K31/555)
- A61K 38/06: Tripeptides
- A61K 38/07: Tetrapeptides
- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/1816: {Erythropoietin [EPO]}
- A61K 38/2013: {IL-2}
- A61K 38/21: Interferons {[IFN]}
- A61K 38/212: {IFN-alpha}
- A61K 38/215: {IFN-beta}
- A61K 38/25: Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
- A61K 47/55: the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- 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
- C07K 5/08: Tripeptides
- C07K 5/081: {the side chain containing O or S as heteroatoms, e.g. Cys, Ser}
- C07K 5/10: Tetrapeptides
- C07K 5/1008: {the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala}
- C07K 7/06: having 5 to 11 amino acids
- 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)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention describes peptides comprising phycocyanobilin (PCB), as well as the medical use of said peptides and that of PCB, due to the neuroprotector and/or neuroregenerative effects identified for them. Furthermore, pharmaceutical combinations of said peptides and of PCB with proteins or other peptides with synergic effect justify their use for ischemic or neurodegenerative CNS disease treatment.

## Claims

### Claim 1

A pharmaceutical combination characterized by its components having a synergic effect and comprising a first component consisting of (i) any of the chromogenic peptides identified as SEQ ID NO:2-SEQ ID NO:5 (PCB-aa) or (ii) phycocyanobilin (PCB), and a second component selected from the group consisting of interferon beta, Interleukin-2 (IL-2), Erythropoietin (EPO), asyaloEPO and Peptide secretagogue of the human growth hormone (GHRP-6).

### Claim 2 (depends on 1)

The combination according to claim 1 wherein said first component is present in an amount of 0.9-3.375 mg of any of the peptides identified as SEQ ID NO:2 to SEQ ID NO:5 per Kg of weight of a treated patient, or 300-750 μg of phycocyanobilin per Kg of weight of a treated patient and the second component is present in a range of 500-5000 ng of the interferon beta.

### Claim 3 (depends on 1)

A method for the prophylaxis or the treatment of ischemia or tissue degeneration, said method comprising administering the pharmaceutical combination of claim 1 to a subject in need thereof.

### Claim 4 (depends on 3)

The method according to claim 3 wherein ischemia or tissue degeneration produces diseases of the CNS that progress with ischemic, or neurodegenerative damage.

### Claim 5 (depends on 1)

A method for the prophylaxis or treatment of ischemic or neurodegenerative CNS diseases, said method comprising administering the pharmaceutical combination of claim 1 to a subject in need thereof.

### Claim 6 (depends on 5)

Method according to claim 5 wherein said combination protects the brain parenchyma damaged as a consequence of acute or chronic diseases.

### Claim 7 (depends on 5)

The method according to claim 5 wherein the combination is administered simultaneously to the same subject during the course of a medical treatment in CNS diseases selected from the group consisting of brain ischemia, multiple sclerosis, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Spinocerebellar ataxia, Huntington's disease and Parkinson's disease.