IP Library Granted Patent US 11,993,646
Granted Patent B2
US 11,993,646 · App. 16/994,837 · Granted May 28, 2024

Compositions and methods for modified b cells expressing reassigned biological agents

Inventors: Roderick A. Hyde (Redmond, WA); Wayne R. Kindsvogel (Seattle, WA); Gary L. McKnight (Bothell, WA)
Assignee: KOTA BIOTHERAPEUTICS, LLC
C07K16/18A61K39/00C07K16/00C07K16/1018C07K16/109C07K16/1271C07K16/3069C07K16/44C12N5/0635G01N33/6854A61K2039/505A61K2039/5156C07K2317/14C07K2317/33C07K2317/76C12N2510/00
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Quick Facts
Patent No.
US 11,993,646
App. No.
16/994,837
Granted
May 28, 2024
Kind
B2
Abstract

Compositions and methods are disclosed herein for producing one or more immunoglobulins in an isolated cytotoxic 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 capable of binding to a first antigen and at least one endogenous secreted immunoglobulin capable of binding to a second antigen, and further capable of expressing at least one exogenously incorporated recombinant B cell receptor that signals for expression of cytotoxic effector molecules.

Claims (36)

1. A modified B cell of expressing:

at least one exogenously incorporated membrane immunoglobulin or a recombinant receptor that at least does one of binding to a first antigen and is stimulated by a first antigen;

at least one exogenously incorporated reassigned biological agent, and

at least one endogenous secreted immunoglobulin reactive to a second antigen.

2. The modified B cell of claim 1 , wherein the at least one exogenously incorporated membrane immunoglobulin includes at least one exogenously incorporated nucleic acid encoding the at least one exogenous membrane immunoglobulin.

3. The modified B cell of claim 2 , wherein the exogenously incorporated nucleic acid encoding the at least one membrane immunoglobulin is integrated in one or more chromosomal loci in the isolated B lymphocyte cell line.

4. The modified B cell of claim 3 , wherein the chromosomal loci include at least one of the Ig H chain or Ig L chain chromosomal loci located on the non-expressed Ig allele.

5. The isolated modified B cell of claim 3 , wherein integration of at least one exogenous nucleic acid encoding the exogenous membrane immunoglobulin includes disruption of expression of the B cell endogenous immunoglobulin.

6. The modified B cell of claim 3 , wherein the at least one exogenously incorporated membrane immunoglobulin or a recombinant receptor that at least does one of binding to the first antigen and is stimulated by a first antigen and effects the production of the at least one endogenous secreted immunoglobulin reactive to the second antigen.

7. The modified B cell of claim 1 , wherein the at least one exogenously incorporated membrane immunoglobulin includes at least two exogenously incorporated nucleic acids encoding the at least one exogenous membrane immunoglobulin.

8. The modified B cell of claim 1 , wherein the at least one exogenously incorporated membrane immunoglobulin includes nucleic acids encoding one heavy chain (H) immunoglobulin and one light chain (L) immunoglobulin.

9. A modified B cell that is modified for expressing:

at least one exogenously incorporated membrane immunoglobulin or recombinant receptor that that one of least binds to a first antigen and is stimulated by a first antigen;

at least one exogenously incorporated reassigned biological agent; and

at least one exogenously incorporated nucleic acid encoding secreted immunoglobulin that at least does one of binding to a second antigen and is stimulated by a second antigen.

10. The isolated modified B cell of claim 9 , wherein the exogenously incorporated nucleic acid encoding the at least one membrane immunoglobulin is integrated in one or more chromosomal loci in the isolated modified B cell.

11. The modified B cell of claim 10 , wherein the chromosomal loci include at least one of the Ig H chain or Ig L chain chromosomal loci.

12. The isolated modified B cell of claim 11 , wherein

integration of at least one exogenous nucleic acid encoding the exogenous membrane immunoglobulin includes disruption of expression of the B cell endogenous immunoglobulin.

13. The modified B cell of claim 9 , wherein the at least one exogenously incorporated membrane immunoglobulin includes at least two exogenously incorporated nucleic acids encoding the at least one exogenous membrane immunoglobulin.

14. The modified B cell of claim 13 , wherein the at least one exogenously incorporated membrane immunoglobulin includes nucleic acids encoding two heavy chain (H) immunoglobulins and two light chain (L) immunoglobulins.

15. The modified B cell of claim 9 , wherein the at least one exogenously incorporated membrane immunoglobulin includes nucleic acids encoding one heavy chain (H) immunoglobulin and one light chain (L) immunoglobulin.

16. The modified B cell of claim 9 , wherein the modified B cell is included in a polyclonal population of B lymphocytes.

17. The modified B cell of claim 9 , wherein the modified B cell is included in a monoclonal population of B lymphocytes.

18. The modified B cell of claim 9 , wherein the exogenously incorporated nucleic acid encoding secreted immunoglobulin is encoded by an exogenously incorporated nucleic acid integrated into at least one chromosomal loci in the modified B cell including one or more non-Ig L or non-Ig H chromosomal loci.

19. The modified B cell of claim 18 , the exogenously incorporated nucleic acid is within a chromosomal locus of the B cell endogenous immunoglobulin H-chain and/or L-chain.

20. A modified B cell capable of for expressing at least one exogenously incorporated membrane immunoglobulin or a recombinant receptor that is reactive to a first antigen;

and at least one endogenous secreted immunoglobulin reactive to a second antigen;

at least one exogenously incorporated reassigned biological agent;

and at least one exogenously incorporated membrane receptor configured to directly or indirectly induce expression of at least one cytotoxic effector molecule.

21. The modified B cell of claim 20 , wherein the membrane receptor configured to directly or indirectly induce at least one cytotoxic effector molecule includes at least one chimeric receptor exhibiting at least a portion of at least one cytokine receptor.

22. An modified B cell for expressing at least one exogenously incorporated membrane immunoglobulin or a recombinant receptor that is reactive to a first antigen;

and at least one exogenous secreted immunoglobulin reactive to a second antigen;

at least one exogenously incorporated reassigned biological agent;

and at least one exogenously incorporated membrane receptor configured to directly or indirectly induce expression of at least one cytotoxic effector molecule.

23. The modified B cell of claim 22 , wherein the membrane receptor configured to directly or indirectly induce at least one cytotoxic effector molecule includes at least one chimeric receptor exhibiting at least a portion of at least one cytokine receptor.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 6, 2021
From: KOTA BIOTHERAPEUTICS, LLC
To: THE INVENTION SCIENCE FUND II, LLC
Reel/Frame 056159/0064 →
Continuity (5)
Continuation 15924898 · Mar 19, 2018
Continuation In Part 15178715 · Jun 10, 2016
Continuation In Part 14549685 · Nov 21, 2014
Continuation 13374351 · Dec 22, 2011
Related Publication 20210095010A1 · Apr 1, 2021