Compounds, methods of screening, and in vitro and in vivo uses involving anti-apoptotic genes and anti-apoptotic gene products

• US 7,449,450 B2
• Filed: 04/13/2005
• Issued: 11/11/2008
• Est. Priority Date: 05/18/1998
• Status: Expired due to Fees

• Current Assignee: ImmunoGen Incorporated
• Original Assignee: ImmunoGen Incorporated
• Inventors: Skaletskaya, Anna, Bartle, Laura M, Goldmakher, Viktor S
• Primary Examiner(s): MOSHER, MARY
• Application Number:
  US11/104,506
• Publication Number:
  US 20050191696A1
• Time in Patent Office: 1,308 Days
• Field of Search: 435/5, 435/6, 530/350, 424/211.1
• US Class Current: 514/44.00R
• 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 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• 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 37/00 Drugs for immunological or allergic disorders
• 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 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: C07K 14/005 from viruses
• CPC Class Codes: C12N 2710/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: G01N 2510/00 Detection of programmed cell death, i.e. apoptosis
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity
• CPC Class Codes: G01N 33/5017 for testing neoplastic activity
• CPC Class Codes: G01N 33/502 for testing non-proliferative effects
• CPC Class Codes: G01N 33/5035 on sub-cellular localization

Abstract

Novel polypeptides having anti-apoptotic activity, and methods of screening for such novel polypeptides having anti-apoptotic activity, and polynucleotides encoding such polypeptides; Compounds that regulate or modulate apoptosis and/or anti-apoptotic activity, such as compounds having anti-apoptotic activity, and such as compounds that induce, restore, or modulate apoptosis and/or inhibit, diminish, or modulate anti-apoptotic activity, methods of screening for such compounds, and methods of using such compounds in the therapeutic treatment of diseases; Methods of treating eukaryotic cells with compounds that regulate or modulate apoptosis and/or anti-apoptotic activity; Methods of enhancing the stability, growth, and/or productivity of eukaryotic cells; Pharmaceutical compositions that regulate or modulate apoptosis and/or anti-apoptotic activity.

Claims

1. A composition comprising a therapeutically effective amount of an agent, which is an antisense oligonucleotide which binds to a polynucleotide which encodes human cytomegalovirus pUL37s, wherein the therapeutically effective amount is an amount that restores apoptosis in CMV-infected cells.

2. The composition of claim 1, wherein said antisense oligonucleotide comprises a phosphorothioate backbone.

4. The composition of claim 1, wherein said antisense oligonucleotide comprises at least 25 consecutive nucleotides of a polynucleotide which encodes human cytomegalovirus pUL37s.

5. The composition of claim 1, wherein said antisense oligonucleotide comprises methylphosphonate moieties.

6. The composition of claim 1, wherein said antisense oligonucleotide is soluble.

7. The composition of claim 1, wherein said antisense oligonucleotide comprises at least one modified internucleoside linkage.

8. The antisense composition of claim 7, wherein the modified internucleoside linkage is a phosphorothioate linkage.

9. The antisense composition of claim 1 wherein said antisense oligonucleotide comprises at least one modified nucleobase.

12. A method for modulating apoptosis, said method comprising:

contacting a eukaryotic cell with an effective amount of a composition according to any one of claims 1 to 9.

3. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier or excipient, and a therapeutically effective amount of an agent, which is an antisense oligonucleotide which binds to a polynucleotide which encodes human cytomegalovirus pUL37s, wherein the therapeutically effective amount is an amount that restores apoptosis in CMV-infected cells.

10. A method for modulating apoptosis in a cell expressing pUL37s, said method comprising:

contacting said cell with a composition comprising a therapeutically effective amount of an agent, wherein said agent is an antisense oligonucleotide which binds to a polynucleotide which encodes human cytomegalovirus pUL37s, wherein the therapeutically effective amount is an amount that restores apoptosis in CMV-infected cells.

11. The method of claim 10, wherein said antisense oligonucleotide comprises a phosphorothioate backbone.

13. The method of claim 10, wherein said composition comprises a pharmaceutically-acceptable carrier or excipient.

14. The method of claim 10, wherein said antisense oligonucleotide comprises at least 25 consecutive nucleotides of a polynucleotide which encodes human cytomegalovirus pUL37s.

15. The method of claim 10, wherein said antisense oligonucleotide comprises methyiphosphonate moieties.

16. The method of claim 10, wherein said antisense oligonucleotide is soluble.

17. The method of claim 10, wherein said antisense oligonucleotide comprises at least one modified internucleoside linkage.

18. The method of claim 10, wherein said antisense oligonucleotide comprises at least one modified internucleoside linkage, wherein said internucleoside linkage is a phosphorothioate linkage.

19. The method of claim 10, wherein said antisense oligonucleotide comprises at least one modified nucleobase.