Long lasting drug formulations

• US 8,586,024 B2
• Filed: 06/30/2011
• Issued: 11/19/2013
• Est. Priority Date: 09/14/2006
• Status: Expired due to Fees

• Current Assignee: Medgenics Medical Israel Ltd.
• Original Assignee: Medgenics Medical Israel Ltd.
• Inventors: Pearlman, Andrew L., Stern, Baruch S.
• Primary Examiner(s): Paras, Jr., Peter
• Assistant Examiner(s): Montanari, David A
• Application Number:
  US13/172,915
• Publication Number:
  US 20120003196A1
• Time in Patent Office: 873 Days
• Field of Search: 424/93.2, 424/93.21
• US Class Current: 424/93.2
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• 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 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61K 47/6901 Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
• CPC Class Codes: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/04 for throat disorders
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• 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: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07K 14/505 : Erythropoietin [EPO]
• CPC Class Codes: C12N 15/86 : Viral vectors
• CPC Class Codes: C12N 15/88 : using microencapsulation, e.g. using amphiphile liposome vesicle
• CPC Class Codes: C12N 2710/10343 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

The present invention is directed to long-lasting therapeutic formulations and their methods of use wherein the formulation comprises a genetically modified micro-organ that comprises a vector which comprises a nucleic acid sequence operably linked to one or more regulatory sequences, wherein the nucleic acid sequence encodes a therapeutic polypeptide, such as erythropoietin or interferon alpha.

Claims

1. A long-lasting therapeutic formulation for implanting into an immunocompetent human subject comprising:

a genetically modified dermal micro-organ, wherein said dermal micro-organ consists essentially of dermal tissue and lacks a complete epidermal layer, wherein said dermal micro-organ is transduced in vitro with a helper-dependent adenoviral vector comprising the nucleic acid sequence set forth in SEQ ID NO;

2, wherein said nucleic acid sequence encodes for interferon and is operably linked to one or more regulatory sequences, wherein said one or more regulatory sequences comprise a CAG promoter, wherein following said transduction the genetically modified dermal micro-organ is maintained ex vivo prior to implantation in order to reduce the immunogenicity of said formulation and wherein implantation of said long-lasting formulation in said immunocompetent human subject provides a beneficial effect selected from the group consisting of;

a. an increase in expression levels of said interferon in the serum compared with pre-implantation basal levels, said increase persisting for greater than one month; and

b. an alleviation of a symptom of a disease or disorder in said subject, wherein said alleviation persists for greater than one month.

2. The formulation of claim 1, wherein said regulatory sequence comprises a SV40 polyadenylation sequence.