Long lasting drug formulations

• US 9,155,749 B2
• Filed: 09/12/2007
• Issued: 10/13/2015
• 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): Singh, Anoop
• Assistant Examiner(s): Montanari, David A
• Application Number:
  US11/898,481
• Publication Number:
  US 20080090777A1
• Time in Patent Office: 2,953 Days
• Field of Search: 435/325, 435/366
• US Class Current: 1/1
• 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 micro-organ is transduced in vitro with a helper-dependent adenoviral (HdAd) vector or with an adeno-associated viral (AAV) vector comprising a nucleic acid sequence encoding a therapeutic erythropoietin polypeptide operably linked to one or more regulatory sequences, wherein said nucleic acid sequence is greater than 95% homologous to SEQ ID No:

1, wherein following said transduction in vitro expression of said therapeutic polypeptide is determined, 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 therapeutic erythropoietin in the subject'"'"'s serum compared with pre-implantation basal levels; 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.

3. The formulation of claim 1 wherein said micro-organ is implanted subcutaneously.

4. The formulation of claim 1, wherein said micro-organ is implanted intradermally.

5. The formulation of claim 1, wherein said one or more regulatory sequences comprise a CAG promoter.

6. The formulation of claim 1, wherein said micro-organ is transduced in vitro with an HdAd vector.

7. The formulation of claim 1, wherein said micro-organ is transduced in vitro with an AAV vector.

8. The formulation of claim 5, wherein the in vitro expression of said therapeutic erythropoietin polypeptide is increased under the control of a CAG promoter compared to a CMV promoter.