IP Library › Granted Patent US 12,589,145
Granted Patent B2
US 12,589,145 · App. 18/166,151 · Granted Mar 31, 2026

Systems to produce B cells genetically modified to express selected antibodies

Inventors: Justin J. Taylor (Seattle, WA); Howell F. Moffett (Seattle, WA)
Assignee: Fred Hutchinson Cancer Center
A61K39/12A61K40/13A61K40/24A61K40/46C07K16/082C07K16/085C07K16/087C07K16/089C07K16/1018C07K16/1027C07K16/1045C07K16/1282C07K16/241C12N5/0635C12N15/86C12N15/907A61K2239/31A61K2239/38C12N15/861C12N2310/20C12N2510/00C12N2750/14143C12N2800/80
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Quick Facts
Patent No.
US 12,589,145
App. No.
18/166,151
Granted
Mar 31, 2026
Kind
B2
Abstract

Systems and methods to genetically modify B cells to express selected antibodies are described. The systems and methods can be used to: obviate the need for classical vaccinations; provide protection against infectious agents for which no vaccinations are currently available; provide protection against infectious agents when patients are otherwise immune-suppressed; and/or provide a benefit provided by a therapeutic antibody, such as in the treatment of autoimmune disorders.

Claims (34)

1 . A genetic construct comprising or encoding (i) a heavy chain promoter, (ii) a signal peptide, (iii) a full-length light chain of a selected antibody; (iv) a flexible linker or a skipping element; (v) a variable region of a heavy chain of the selected antibody; and (vi) a splice junction comprising the sequence CAGGTAAGT or CAGGTGAGT and 40-80 base pairs of the intron following the last exon of a variable-diversity-joining (VDJ).

2 . The genetic construct of claim 1 , wherein the flexible linker is between the full-length light chain of the selected antibody and the variable region of the heavy chain of the selected antibody.

3 . The genetic construct of claim 1 , wherein the flexible linker is encoded by the nucleotide sequence as set forth in SEQ ID NO: 116; has the amino acid sequence as set forth in one of SEQ ID NOs: 122, 180-184; and/or is a Gly-Ser linker comprising 50-80 amino acids.

4 . The genetic construct of claim 1 , wherein the skipping element is between the full-length light chain of the selected antibody and the variable region of the heavy chain of the selected antibody.

5 . The genetic construct of claim 1 , wherein the skipping element comprises an internal ribosome entry site (IRES) or a self-cleaving peptide having the sequence as set forth in SEQ ID NOs: 176, 177, 178, or 179.

6 . The genetic construct of claim 1 , wherein the heavy chain promoter is IgVH1-69 or J558H10.

7 . The genetic construct of claim 1 , wherein the signal peptide is selected from the sequence as set forth in one of SEQ ID NOs: 118, 134, and 185-194.

8 . The genetic construct of claim 1 , wherein the signal peptide is a signal peptide of a human IgH heavy chain or a human IgL light chain.

9 . The genetic construct of claim 1 , wherein the genetic construct further comprises homology arms.

10 . The genetic construct of claim 9 , wherein the homology arms have the sequence as set forth in SEQ ID NO: 90-101, 110, 125, 127, 140, 142, 143, 153, 170, 171, 173, 174, 278, or 279.

11 . The genetic construct of claim 1 , wherein the genetic construct further encodes a tag having the sequence as set forth in SEQ ID NOs: 122, 195, 196, 197, 198, 199, 200, 201, 202, 203, or 204.

12 . The genetic construct of claim 1 , wherein the selected antibody is

an anti-RSV antibody comprising

(a) a variable heavy chain comprising the sequence as set forth in SEQ ID NO: 138 and a variable light chain comprising the sequence as set forth in SEQ ID NO: 136,

(b) a variable heavy chain comprising the sequence as set forth in SEQ ID NO: 138 and a variable light chain comprising the sequence as set forth in SEQ ID NO: 205,

(c) a variable heavy chain comprising the sequence as set forth in SEQ ID NO: 123 and a light chain comprising the sequence as set forth in SEQ ID NO: 120, or

(d) a variable heavy chain comprising the sequence as set forth in SEQ ID NO: 123 and a variable light chain comprising the sequence as set forth in SEQ ID NO: 206;

an anti-human immunodeficiency virus (HIV) antibody comprising a variable heavy chain comprising the sequence as set forth in SEQ ID NO: 150 and a variable light chain comprising the sequence as set forth in SEQ ID NO: 149;

an anti-pertussis antibody comprising a variable heavy chain comprising the sequence as set forth in SEQ ID NO: 235 and a variable light chain comprising the sequence as set forth in SEQ ID NO: 236;

an anti-influenza virus antibody comprising a variable heavy chain comprising the sequence as set forth in SEQ ID NO: 159 and a variable light chain comprising the sequence as set forth in SEQ ID NO: 158;

anti-Epstein Barr virus (EBV) antibody comprising a variable heavy chain comprising the sequence as set forth in SEQ ID NO: 168 and a variable light chain comprising the sequence as set forth in SEQ ID NO: 166; or

an anti-tumor necrosis factor (TNF) antibody comprising a variable heavy chain comprising the sequence as set forth in SEQ ID NO: 254 and a variable light chain comprising the sequence as set forth in SEQ ID NO: 255.

13 . A kit comprising a genetic construct of claim 1 and a gRNA that binds a genomic region comprising SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

14 . The kit of claim 13 , wherein the gRNA has the sequence as set forth in

SEQ ID NO: 88, 89, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, or 307 when the genomic region comprises SEQ ID NO: 1;

SEQ ID NO: 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, or 327 when the genomic region comprises SEQ ID NO: 2;

SEQ ID NO: 87, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, or 346 when the genomic region comprises SEQ ID NO: 3; or

SEQ ID NO: 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, or 366 when the genomic region comprises SEQ ID NO: 4.

15 . The kit of claim 13 , further comprising a nuclease.

16 . The kit of claim 15 , wherein the nuclease is Cas9 or Cpf1.

17 . The kit of claim 13 , further comprising a nanoparticle or adeno-associated viral vector.

18 . The kit of claim 15 , wherein the gRNA and nuclease are associated with a nanoparticle and the genetic construct is part of an adeno-associated viral vector.

19 . Am isolated B cell comprising the genetic construct of claim 1 , wherein the genetic construct is inserted into a genomic region having the sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

20 . The B cell of claim 19 , wherein the B cell is an antibody-secreting B cell, a memory B cell, a naïve B cell, a B 1 B cell or a marginal zone B cell.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 7, 2023
From: TAYLOR, JUSTIN J.; MOFFETT, HOWELL F.
To: FRED HUTCHINSON CANCER RESEARCH CENTER
Reel/Frame 064182/0549 →
MERGER AND CHANGE OF NAME Recorded Jul 7, 2023
From: FRED HUTCHINSON CANCER RESEARCH CENTER; SEATTLE CANCER CARE ALLIANCE
To: FRED HUTCHINSON CANCER CENTER
Reel/Frame 064182/0570 →
Continuity (5)
Continuation 16757707
Provisional Application 62623371 · Jan 29, 2018
Provisional Application 62580303 · Nov 1, 2017
Provisional Application 62575275 · Oct 20, 2017
Related Publication 20230250159A1 · Aug 10, 2023
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