Granted Patent
B2
US 12,269,854 · App. 16/952,848 · Granted Apr 8, 2025
Multi-chain chimeric polypeptides and uses thereof
Assignee:
ImmunityBio, Inc.
C07K14/5434C07K14/54C07K14/5418C07K14/71C07K14/7155C07K14/745C07K16/283C07K2317/622C07K2319/02C07K2319/03C07K2319/30
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Abstract
Provided herein are multi-chain chimeric polypeptides that include: (a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.
Claims (79)
1. A multi-chain chimeric polypeptide comprising:
(a) a first chimeric polypeptide comprising:
(i) a first target-binding domain;
(ii) a soluble tissue factor domain comprising a sequence at least 80% identical to SEQ ID NO: 1; and
(iii) a first domain of a pair of affinity domains comprising a sequence that is at least 80% identical to SEQ ID NO: 14;
(b) a second chimeric polypeptide comprising:
(i) a second domain of a pair of affinity domains comprising a sequence that is at least 80% identical to SEQ ID NO: 28; and
(ii) a second target-binding domain,
wherein the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains; and
wherein (A) the first target-binding domain comprises a sequence at least 80% identical to SEQ ID NO: 16 and the second target-binding domain comprises a first sequence that is at least 80% identical to SEQ ID NO: 66 and a second sequence that is at least 80% identical to SEQ ID NO: 68, or (B) the first target-binding domain comprises a first sequence that is at least 80% identical to SEQ ID NO: 66 and a second sequence that is at least 80% identical to SEQ ID NO: 68, and the second target-binding domain comprises a sequence at least 80% identical to SEQ ID NO: 16.
2. The multi-chain chimeric polypeptide of claim 1 , wherein the first target-binding domain and the soluble tissue factor domain directly abut each other in the first chimeric polypeptide.
3. The multi-chain chimeric polypeptide of claim 1 , wherein the first chimeric polypeptide further comprises a linker sequence between the first target-binding domain and the soluble tissue factor domain in the first chimeric polypeptide.
4. The multi-chain chimeric polypeptide of claim 1 , wherein the soluble tissue factor domain and the first domain of the pair of affinity domains directly abut each other in the first chimeric polypeptide.
5. The multi-chain chimeric polypeptide of claim 1 , wherein the first chimeric polypeptide further comprises a linker sequence between the soluble tissue factor domain and the first domain of the pair of affinity domains in the first chimeric polypeptide.
6. The multi-chain chimeric polypeptide of claim 1 , wherein the second domain of the pair of affinity domains and the second target-binding domain directly abut each other in the second chimeric polypeptide.
7. The multi-chain chimeric polypeptide of claim 1 , wherein second chimeric polypeptide further comprises a linker sequence between the second domain of the pair of affinity domains and the second target-binding domain in the second chimeric polypeptide.
8. The multi-chain chimeric polypeptide of claim 1 , wherein the soluble tissue factor domain is a soluble human tissue factor domain.
9. The multi-chain chimeric polypeptide of claim 8 , wherein the human soluble tissue factor domain does not initiate blood coagulation.
10. The multi-chain chimeric polypeptide of claim 1 , wherein the first target-binding domain comprises a sequence at least 80% identical to SEQ ID NO: 16 and the second target-binding domain comprises a first sequence that is at least 80% identical to SEQ ID NO: 66 and a second sequence that is at least 80% identical to SEQ ID NO: 68.
11. The multi-chain chimeric polypeptide of claim 1 , wherein the first chimeric polypeptide comprises a sequence that is at least 80% identical to SEQ ID NO: 70 and the second chimeric polypeptide comprises a sequence that is at least 80% identical to SEQ ID NO: 74.
12. The multi-chain chimeric polypeptide of claim 10 , wherein the first and second sequence are separated by a linker.
13. The multi-chain chimeric polypeptide of claim 12 , wherein the linker comprises a sequence of SEQ ID NO: 7.
14. The multi-chain chimeric polypeptide of claim 1 , wherein the first chimeric polypeptide comprises a sequence that is at least 80% identical to SEQ ID NO: 72 and the second chimeric polypeptide comprises a sequence that is at least 80% identical to SEQ ID NO: 76.
15. The multi-chain chimeric polypeptide of claim 1 , wherein the first chimeric polypeptide comprises a sequence that is at least 90% identical to SEQ ID NO: 72 and the second chimeric polypeptide comprises a sequence that is at least 90% identical to SEQ ID NO: 76.
16. The multi-chain chimeric polypeptide of claim 1 , wherein the first chimeric polypeptide comprises a sequence that is at least 96% identical to SEQ ID NO: 72 and the second chimeric polypeptide comprises a sequence that is at least 96% identical to SEQ ID NO: 76.
17. The multi-chain chimeric polypeptide of claim 1 , wherein the first chimeric polypeptide comprises a sequence of SEQ ID NO: 72 and the second chimeric polypeptide comprises a sequence of SEQ ID NO: 76.
18. The multi-chain chimeric polypeptide of claim 1 , wherein the first chimeric polypeptide comprises a sequence of SEQ ID NO: 70 and the second chimeric polypeptide comprises a sequence of SEQ ID NO: 74.
19. A composition comprising the multi-chain chimeric polypeptide of claim 1 .
20. The composition of claim 19 , wherein the composition is a pharmaceutical composition.
21. The multi-chain chimeric polypeptide of claim 1 , wherein:
the first target-binding domain comprises a sequence that is at least 90% identical to SEQ ID NO: 16;
the soluble tissue factor domain comprises a sequence that is at least 90% identical to SEQ ID NO: 1;
the first domain of the pair of affinity domains comprises a sequence that is at least 90% identical to SEQ ID NO: 14;
the second target-binding domain comprises a first sequence that is at least 90% identical to SEQ ID NO: 66 and a second sequence that is at least 90% identical to SEQ ID NO: 68; and
the second domain of the pair of affinity domains comprises a sequence that is at least 90% identical to SEQ ID NO: 28.
22. The multi-chain chimeric polypeptide of claim 1 , wherein:
the first target-binding domain comprises a sequence that is at least 95% identical to SEQ ID NO: 16;
the soluble tissue factor domain comprises a sequence that is at least 95% identical to SEQ ID NO: 1;
the first domain of the pair of affinity domains comprises a sequence that is at least 95% identical to SEQ ID NO: 14;
the second target-binding domain comprises a first sequence that is at least 95% identical to SEQ ID NO: 66 and a second sequence that is at least 95% identical to SEQ ID NO: 68; and
the second domain of the pair of affinity domains comprises a sequence that is at least 95% identical to SEQ ID NO: 28.
23. The multi-chain chimeric polypeptide of claim 1 , wherein:
the first target-binding domain comprises SEQ ID NO: 16;
the soluble tissue factor domain comprises SEQ ID NO: 1;
the first domain of the pair of affinity domains comprises SEQ ID NO: 14;
the second target-binding domain comprises a first sequence of SEQ ID NO: 66 and a second sequence of SEQ ID NO: 68; and
the second domain of the pair of affinity domains comprises SEQ ID NO: 28.
24. The multi-chain chimeric polypeptide of claim 1 , wherein:
the first chimeric polypeptide comprises a sequence that is at least 90% identical to SEQ ID NO: 70; and
the second chimeric polypeptide comprises a sequence that is at least 90% identical to SEQ ID NO: 74.
25. The multi-chain chimeric polypeptide of claim 1 , wherein:
the first chimeric polypeptide comprises a sequence that is at least 95% identical to SEQ ID NO: 70; and
the second chimeric polypeptide comprises a sequence that is at least 95% identical to SEQ ID NO: 74.
26. The multi-chain chimeric polypeptide of claim 21 , wherein the first and second sequence are separated by a linker.
27. The multi-chain chimeric polypeptide of claim 22 , wherein the first and second sequence are separated by a linker.
28. The multi-chain chimeric polypeptide of claim 23 , wherein the first and second sequence are separated by a linker.
29. The multi-chain chimeric polypeptide of claim 1 , wherein the first target-binding domain comprises a first sequence that is at least 80% identical to SEQ ID NO: 66 and a second sequence that is at least 80% identical to SEQ ID NO: 68, and the second target-binding domain comprises a sequence at least 80% identical to SEQ ID NO: 16.
30. The multi-chain chimeric polypeptide of claim 29 , wherein the first and second sequence are separated by a linker.
31. The multi-chain chimeric polypeptide of claim 1 , wherein:
the first target-binding domain comprises a first sequence that is at least 90% identical to SEQ ID NO: 66 and a second sequence that is at least 90% identical to SEQ ID NO: 68;
the soluble tissue factor domain comprises a sequence that is at least 90% identical to SEQ ID NO: 1;
the first domain of the pair of affinity domains comprises a sequence that is at least 90% identical to SEQ ID NO: 14;
the second target-binding domain comprises a sequence at least 90% identical to SEQ ID NO: 16; and
the second domain of the pair of affinity domains comprises a sequence that is at least 90% identical to SEQ ID NO: 28.
32. The multi-chain chimeric polypeptide of claim 31 , wherein the first and second sequence are separated by a linker.
33. The multi-chain chimeric polypeptide of claim 1 , wherein:
the first target-binding domain comprises a first sequence that is at least 95% identical to SEQ ID NO: 66 and a second sequence that is at least 95% identical to SEQ ID NO: 68;
the soluble tissue factor domain comprises a sequence that is at least 95% identical to SEQ ID NO: 1;
the first domain of the pair of affinity domains comprises a sequence that is at least 95% identical to SEQ ID NO: 14;
the second target-binding domain comprises a sequence at least 95% identical to SEQ ID NO: 16; and
the second domain of the pair of affinity domains comprises a sequence that is at least 95% identical to SEQ ID NO: 28.
34. The multi-chain chimeric polypeptide of claim 33 , wherein the first and second sequence are separated by a linker.
35. The multi-chain chimeric polypeptide of claim 1 , wherein:
the first target-binding domain comprises a first sequence of SEQ ID NO: 66 and a second sequence of SEQ ID NO: 68;
the soluble tissue factor domain comprises SEQ ID NO: 1;
the first domain of the pair of affinity domains comprises SEQ ID NO: 14;
the second target-binding domain comprises SEQ ID NO: 16; and
the second domain of the pair of affinity domains comprises SEQ ID NO: 28.
36. The multi-chain chimeric polypeptide of claim 35 , wherein the first and second sequence are separated by a linker.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 17, 2024
From: HCW BIOLOGICS INC.
To: IMMUNITYBIO, INC.
Reel/Frame 068014/0474 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 23, 2020
From: WONG, HING
To: HCW BIOLOGICS, INC.
Reel/Frame 054442/0144 →
Continuity (12)
Provisional Application
62881088
· Jul 31, 2019
Provisional Application
62817230
· Mar 12, 2019
Provisional Application
62817241
· Mar 12, 2019
Provisional Application
62816683
· Mar 11, 2019
Provisional Application
62749506
· Oct 23, 2018
Provisional Application
62749007
· Oct 22, 2018
Provisional Application
62746832
· Oct 17, 2018
Provisional Application
62724969
· Aug 30, 2018
Provisional Application
62725043
· Aug 30, 2018
Provisional Application
62725010
· Aug 30, 2018
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