IDEOTYPICALLY MODULATED PHARMACOEFFECTORS FOR SELECTIVE CELL TREATMENT

• US 20110293639A1
• Filed: 05/26/2011
• Published: 12/01/2011
• Est. Priority Date: 05/31/2010
• Status: Active Grant

• Current Assignee: Imperium Biotechnologies, Inc.
• Original Assignee: Imperium Biotechnologies, Inc.
• Inventors: Orme, Jacob
• Granted Patent: US 8,518,409 B2
• Time in Patent Office: Days
• US Class Current: 424/183.1
• CPC Class Codes: A61K 38/4873 Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 16/08 against material from viruses
• CPC Class Codes: C07K 16/12 against material from bacteria
• CPC Class Codes: C07K 16/20 from protozoa
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/30 : from tumour cells
• CPC Class Codes: C12N 5/0602 : Vertebrate cells

Abstract

In a method embodiment, a method includes introducing a plurality of Ideotypically Modulated Pharmacoeffectors (IMP) into a population of cells. Each IMP may include a detection domain and an activation domain. One or more epitopes is bound by the detection domain. The activation domain is activated in response to the binding. Applications may include but are not limited to viral infections, other intracellular infections, cancers, vector-borne diseases, autoimmune diseases, cellular diseases, cellular enhancement, and research.

Claims

1. A method comprising:

introducing, into a population of cells, instructions for the manufacture of a plurality of Ideotypically Modulated Pharmacoeffectors (IMPs), each of the plurality of manufactured IMPs comprising;

a detection domain that has affinity for an epitope, and

an activation domain coupled to the detection domain;

wherein the detection domain of each IMP of a subset of the plurality of manufactured IMPs is configured to bind to one or more epitopes; and

wherein the activation domain of each IMP of the subset of the plurality of manufactured IMPs is configured to activate and cause a downstream effect in a population of cells.

2. The method of claim 1, wherein the instructions are encoded on a plasmid.

3. The method of claim 1, wherein the population of cells comprises a blood stream.

4. The method of claim 1, wherein the population of cells comprises a tissue culture.

5. The method of claim 1, wherein the detection domain has an affinity for epitopes found in or on cells of interest.

6. The method of claim 1, wherein the activation domain comprises Procaspase-9.

7. The method of claim 1, wherein the activating of the activation domain comprises binding a subset of the plurality of IMPs to adjacent epitopes, the binding of the subset of the plurality of IMPs causing the activation domains of the subset of the plurality of IMPs to interact with each other.

8. A method comprising:

introducing a plurality of engineered Ideotypically Modulated Pharmacoeffectors (IMPs) into a population of cells, each IMP comprising;

a detection domain that has affinity for an epitope, and

an activation domain coupled to the detection domain;

binding the detection domain of each IMP of a subset of the plurality of IMPs to one or more epitopes; and

activating the activation domain of each IMP of the subset of the plurality of IMPs, the activating causing a downstream effect in each cell of at least a subset of the population of cells.

9. The method of claim 8, wherein the downstream effect comprises termination of each cell of the subset of the plurality of cells.

10. The method of claim 8, wherein the population of cells comprises a blood stream.

11. The method of claim 8, wherein the population of cells comprises a tissue culture.

12. The method of claim 8, further comprising conjugating the detection domain with the activation domain using a linker molecule.

13. The method of claim 8, wherein the activating of the activation domain comprises binding a subset of the plurality of IMPs to adjacent epitopes, the binding of the subset of the plurality of IMPs causing the activation domains of the subset of the plurality of IMPs to interact with each other.

14. The method of claim 8, wherein the activation domain comprises:

a porous polymer pouch containing effector molecules; and

a holder molecule that localizes the detection domains of the plurality of IMPs to the pores of the pouch; and

wherein the binding the detection domain of each IMP of a subset of the plurality of IMPs to one or more epitopes further comprises;

dissociating of the holder molecule, and releasing the effector molecules.

15. A system for ideotype-specific treatments, the system comprising:

a plurality of engineered, nonnaturally occurring Ideotypically Modulated Pharmacoeffectors (IMPS), each IMP comprising;

a detection domain that has affinity for an epitope, and

an activation domain coupled to the detection domain, the activation domain configured when activated to cause a downstream effect in a population of cells.

16. The system of claim 15, further comprising a linker molecule that conjugates the detection domain and the activation domain.

17. The system of claim 15, wherein the detection domain of each IMP comprises an antibody fragment.

18. The system of claim 15, wherein the detection domain of each IMP comprises a nucleotide sequence.

19. The system of claim 15, wherein the detection domain of each IMP comprises an antigen against which antigen receptors of a clonal subpopulation of cells are specific.

20. The system of claim 15, wherein the activation domain of each IMP comprises inactive Caspase-9 monomer.

21. The system of claim 15, wherein the activation domain of each IMP comprises a subunit of a bioactive molecule.

22. The system of claim 15, wherein the activation domain of each IMP comprises either a pro-toxin or a toxin-converting enzyme.

23. The system of claim 15, wherein the activating of the activation domain comprises binding a subset of the plurality of IMPs to adjacent epitopes, the binding of the subset of the plurality of IMPs causing the activation domains of the subset of the plurality of IMPs to interact with each other.

24. A system for ideotype-specific treatments, the system comprising:

instructions for the manufacture of a plurality of Ideotypically Modulated Pharmacoeffectors (IMPs), each of the plurality of manufactured IMPs comprising;

a detection domain that has affinity for an epitope, and

an activation domain coupled to the detection domain;

wherein the detection domain of each IMP of a subset of the plurality of manufactured IMPs is configured to bind to one or more epitopes; and

wherein the activation domain of each IMP of the subset of the plurality of manufactured IMPs is configured to activate and cause a downstream effect in a population of cells.

25. The system of claim 24, wherein the instructions are encoded on a plasmid.

26. The system of claim 24, wherein detection domain(s) and activation domain(s) self-assemble to produce functional IMPs.

27. The system of claim 24, wherein self-assembly of IMPs is accomplished by affinity of a ribonucleoprotein subunit to a specific nucleotide sequence.

28. The system of claim 24, wherein the activating of the activation domain comprises binding a subset of the plurality of IMPs to adjacent epitopes, the binding of the subset of the plurality of IMPs causing the activation domains of the subset of the plurality of IMPs to interact with each other.

29. The system of claim 24, wherein the detection domain may be altered in its affinity such that the produced IMP becomes employable against a mutated target.