IP Library Granted Patent US 9,512,213
Granted Patent B2
US 9,512,213 · App. 14/549,685 · Granted Dec 6, 2016

Compositions and methods including recombinant B lymphocyte cell line including an exogenously incorporated nucleic acid expressing an exogenous membrane immunoglobulin reactive to a first antigen and including an endogenous gene expressing an endogenous secreted immunoglobulin reactive to a second antigen

Inventors: Roderick A. Hyde (Redmond, WA); Wayne R. Kindsvogel (Seattle, WA)
Assignee: Elwha LLC
C07K16/18A61K39/00C07K16/00C07K16/109C07K16/1018C07K16/1271C07K16/3069C07K16/44C12N5/0635G01N33/6854A61K2039/505A61K2039/5156C07K2317/14C07K2317/76C12N2510/00
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Quick Facts
Patent No.
US 9,512,213
App. No.
14/549,685
Granted
Dec 6, 2016
Kind
B2
Abstract

Compositions and methods are disclosed herein for producing one or more immunoglobulins in an isolated B lymphocyte cell line. An isolated cell line includes an isolated B lymphocyte cell line capable of expressing at least one exogenously incorporated membrane immunoglobulin reactive to a first antigen and at least one endogenous secreted immunoglobulin reactive to a second antigen.

Claims (36)

1. A method for treating a disease in a vertebrate subject with an immunotherapeutic product comprising:

isolating from a vertebrate subject exposed to at least one second antigen, a B lymphocyte cell expressing at least one endogenous secreted immunoglobulin reactive to the at least one second antigen;

introducing into the isolated B lymphocyte cell at least one exogenous membrane immunoglobulin reactive to at least one first antigen to produce a recombinant B lymphocyte cell;

selecting the recombinant B lymphocyte cell expressing the membrane immunoglobulin reactive to the at least one first antigen and expressing the at least one endogenous secreted immunoglobulin reactive to the at least one second antigen; and

administering a therapeutically effective amount of said recombinant B lymphocyte cell to one or more vertebrate subjects afflicted with disease.

2. The method of claim 1 further including:

administering the at least one first antigen to stimulate the recombinant B lymphocyte cell line; and

testing for the presence of the at least one endogenous secreted immunoglobulin

reactive to the at least one second antigen in the recombinant B lymphocyte cell line.

3. A method for treating a disease in a vertebrate subject with an immunotherapeutic product comprising:

introducing into at least one isolated B lymphocyte cell line at least one exogenous membrane immunoglobulin reactive to at least one first antigen to produce at least one first isolated B lymphocyte cell line;

selecting the at least one first isolated B lymphocyte cell line expressing the membrane immunoglobulin reactive to the at least one first antigen;

introducing into the at least one first isolated B lymphocyte cell line at least one exogenous nucleic acid encoding one or more secreted immunoglobulins reactive to at least one second antigen to produce at least one isolated recombinant B lymphocyte cell line;

selecting the at least one isolated recombinant B lymphocyte cell line expressing the secreted one or more immunoglobulin reactive to the at least one second antigens; and

administering a therapeutically effective amount of said least one isolated recombinant B lymphocyte cell line to one or more vertebrate subjects afflicted with disease.

4. The method of claim 3 further including:

administering the at least one first antigen to stimulate the at least one isolated recombinant B lymphocyte cell line; and

testing for the presence of the one or more secreted immunoglobulin reactive to the at least one second antigen in the at least one isolated recombinant B lymphocyte cell line.

5. A method for treating a disease in a vertebrate subject with an immunotherapeutic product comprising:

introducing into at least one first isolated B lymphocyte cell line at least one exogenous nucleic acid encoding one or more secreted immunoglobulins reactive to at least one first antigen to produce at least one isolated recombinant B lymphocyte cell line;

selecting the at least one isolated recombinant B lymphocyte cell line expressing the secreted one or more immunoglobulin reactive to the at least one first antigens;

introducing into the at least one isolated B lymphocyte cell line at least one exogenous membrane immunoglobulin reactive to at least one second antigen to produce at least one first isolated B lymphocyte cell line;

selecting the at least one first isolated B lymphocyte cell line expressing the membrane immunoglobulin reactive to the at least one second antigen;

and administering a therapeutically effective amount of said isolated B lymphocyte cell line to the vertebrate subject afflicted with disease.

6. The method of claim 1 , further including administering to the vertebrate subject the at least one first antigen to stimulate the isolated B lymphocyte cell line to produce the at least one endogenous secreted immunoglobulin reactive to the at least one second antigen.

7. The method of claim 6 , further including confirming the presence of the at least one endogenous secreted immunoglobulin reactive to the at least one second antigen in a bloodstream of the vertebrate subject.

8. The method of claim 1 , wherein the recombinant B lymphocyte cell line is autologous to one of the one or more vertebrate subjects.

9. The method of claim 1 , wherein the recombinant B lymphocyte cell line is allogeneic to the one or more vertebrate subjects.

10. The method of claim 1 , further including introducing into the at least one isolated recombinant B lymphocyte cell line at least one exogenous nucleic acid sequence encoding one or more secreted immunoglobulins reactive to at least one third antigen to produce at least one isolated second recombinant B lymphocyte cell line.

11. The method of claim 10 , further including selecting the at least one isolated second recombinant B lymphocyte cell line expressing the at least one secreted immunoglobulin reactive to the at least one second antigen and the at least one secreted immunoglobulin reactive to the at least one third antigen.

12. The method of claim 1 , wherein the at least one B lymphocyte includes at least one of a naïve B lymphocyte, an immature B lymphocyte, a transitional B lymphocyte, a mature B lymphocyte, a follicular B lymphocyte, a memory B lymphocyte, a plasmablast, or a plasma cell.

13. The method of claim 3 , further including administering the at least one first antigen to stimulate the at least one isolated recombinant B lymphocyte cell line to produce the one or more exogenous secreted immunoglobulin reactive to the at least one second antigen.

14. The method of claim 3 , further including introducing into the at least one isolated recombinant B lymphocyte cell line at least one exogenous nucleic acid encoding one or more secreted immunoglobulins reactive to at least one third antigen to produce at least one isolated second recombinant B lymphocyte cell line.

15. The method of claim 14 , further including selecting the at least one isolated second recombinant B lymphocyte cell line expressing at least one of the secreted immunoglobulin reactive to the at least one second antigen and the secreted immunoglobulin reactive to the at least one third antigen.

16. The method of claim 5 , further including administering to the vertebrate subject the at least one first antigen to stimulate the isolated B lymphocyte cell line to produce the at least one endogenous secreted immunoglobulin reactive to the at least one second antigen.

17. The method of claim 16 , further including confirming the presence of the at least one endogenous secreted immunoglobulin reactive to the at least one second antigen in a bloodstream of the vertebrate subject.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 6, 2021
From: KOTA BIOTHERAPEUTICS, LLC
To: THE INVENTION SCIENCE FUND II, LLC
Reel/Frame 056159/0064 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 13, 2019
From: THE INVENTION SCIENCE FUND II, LLC
To: KOTA BIOTHERAPEUTICS, LLC
Reel/Frame 050995/0470 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 29, 2019
From: ELWHA LLC
To: THE INVENTION SCIENCE FUND II, LLC
Reel/Frame 050216/0254 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 6, 2015
From: HYDE, RODERICK A.; KINDSVOGEL, WAYNE R.
To: ELWHA LLC
Reel/Frame 035339/0238 →
Continuity (2)
Continuation 13374351 · Dec 22, 2011
Related Publication 20150203572A1 · Jul 23, 2015