IP Library › Granted Patent US 9,845,345

Granted Patent B2

US 9,845,345 · App. 15/157,291 · Granted Dec 19, 2017

SIRP polypeptide compositions and methods of use

Inventors: Aaron Michael Ring (Palo Alto, CA); Roy Louis Maute (San Francisco, CA); Andrew Curtis Kruse (Roslindale, MA); Aashish Manglik (Menlo Park, CA); Kenneth S. Lin (Los Altos, CA)

Assignee: AB INITIO BIOTHERAPEUTICS, INC.

C07K14/55 C07K14/70596 C07K2319/00 C07K2319/21 C07K2319/24 C07K2319/30 C07K2319/50

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Quick Facts

Patent No.: US 9,845,345
App. No.: 15/157,291
Granted: Dec 19, 2017
Kind: B2

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Abstract

Provided herein are SIRP-gamma, SIRP-beta or SIRP-beta2 decoy polypeptides for immunotherapy and/or treatment of cancer, anemia, transplant, asthma, allergy, auto-immune disease, and viral infection.

Claims (150)

1. A polypeptide comprising a SIRP-gamma polypeptide consisting of the sequence EEELQX 1 IQPEKLLLVTVGKTATLHCTX 2 TSX 3 X 4 PX 5 GPX 6 X 7 WFRGX 8 GPGRX 9 LIYNX 10 X 11 X 12 GX 13 FPRVTTVSDX 14 X 15 KRNNMDFSIRISSITPADVGTYYCX 16 KFRKGX 17 PEX 18 VEFK SGPGTEMALGAKPS (SEQ ID NO: 2), wherein X 1 is M, I, L or F; X 2 is F, I, or L; X 3 is L, I, V, H, N or D; X 4 is F, I, L or V; X 5 is V, I, L, P, T or A; X 6 is V or I; X 7 is L or Q; X 8 is V or A; X 9 is E or V; X 10 is Q, P, L, V, A or E; X 11 is K or R; X 12 is E, D, K, N, Q or H; X 13 is H, P or R; X 14 is L, I, V, P, T, A, R, S or G; X 15 is T, I, N, F, S, Y, V, A or D; X 16 is V or I; X 17 is S, R, N, K, T, I or M; and X 18 is N, K, D, E, H or Q, and wherein the SIRP-gamma polypeptide binds CD47.

2. The polypeptide of claim 1 , wherein the SIRP-gamma polypeptide comprises a sequence selected from one of

(SEQ ID NO: 3)

EEELQIIQPEKLLLVTVGKTATLHCTITSLFPVGPVLWFRGVGPGRVLIY

NQRQGPFPRVTTVSDTTKRNNMDFSIRISSITPADVGTYYCIKFRKGSPE

NVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 4)

EEELQIIQPEKLLLVTVGKTATLHCTITSLFPVGPIQWFRGVGPGRVLIY

NQRDGPFPRVTTVSDGTKRNNMDFSIRISSITPADVGTYYCVKFRKGTPE

DVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 5)

EEELQIIQPEKLLLVTVGKTATLHCTITSLFPVGPIQWFRGVGPGRVLIY

NQKDGPFPRVTTVSDGTKRNNMDFSIRISSITPADVGTYYCVKFRKGSPE

DVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 6)

EEELQIIQPEKLLLVTVGKTATLHCTITSLFPVGPIQWFRGVGPGRVLIY

NQKDGHFPRVTTVSDGTKRNNMDFSIRISSITPADVGTYYCVKFRKGSPE

DVEFKSGPGTEMALGAKPS;

and

(SEQ ID NO: 7)

EEELQIIQPEKLLLVTVGKTATLHCTITSLFPVGPIQWFRGAGPGRVLIY

NQRDGPFPRVTTVSDGTKRNNMDFSIRISSITPADVGTYYCIKFRKGTPE

DVEFKSGPGTEMALGAKPS.

3. The polypeptide of claim 1 , wherein the polypeptide blocks binding of CD47 to a ligand.

4. The polypeptide of claim 3 , wherein the ligand is SIRP-alpha, SIRP-gamma, or thrombospondin-1.

5. The polypeptide of claim 1 , wherein the polypeptide binds to a cell which expresses CD47.

6. The polypeptide of claim 5 , wherein the cell is a tumor cell, virally infected cell, bacterially infected cell, damaged red blood cell, arterial plaque cell, fibrotic tissue cell, a healthy normal cell such as hematopoietic stem cell, a healthy myeloid or lymphoid precursor cell, or a healthy differentiated hematopoietic cell type such as T, B, plasma, or NK cell.

7. The polypeptide of claim 1 , wherein the polypeptide further comprises an opsonizing antibody to enable phagocytosis or ADCC of a cell expressing CD47, wherein the cell is a tumor cell, virally infected cell, bacterially infected cell, damaged red blood cell, arterial plaque cell, fibrotic tissue cell, healthy normal cell such as hematopoietic stem cell, healthy myeloid or lymphoid precursor cell or healthy differentiated hematopoietic cell type such as T, B, plasma, or NK cells.

8. The polypeptide of claim 1 , wherein the SIRP-gamma polypeptide is multimeric.

9. The polypeptide of claim 1 , wherein the SIRP-gamma polypeptide is monomeric.

10. The polypeptide of claim 1 , wherein the polypeptide further comprises a detectable label.

11. The polypeptide of claim 1 , wherein the polypeptide has increased occupancy relative to a wildtype SIRP-gamma.

12. The polypeptide of claim 1 , wherein the polypeptide has increased persistence relative to a wildtype SIRP-gamma.

13. The polypeptide of claim 1 , wherein the SIRP-gamma polypeptide comprises the sequence EEELQIIQPEKLLLVTVGKTATLHCTITSLFPVGPIQWFRGVGPGRVLIYNQREGPFPRVTT VSDGTKRNNMDFSIRISSITPADVGTYYCVKFRKGSPEDVEFKSGPGTEMALGAKPS (SEQ ID NO: 13).

14. The polypeptide of claim 1 , wherein the SIRP-gamma polypeptide comprises one of the following sequences:

(SEQ ID NO: 8)

EEELQIIQPEKLLLVTVGKTATLHCTITSHFPVGPIQWFRGVGPGRVLIYNQKDGHFPRVTTVSDGTKR

NNMDFSIRISSITPADVGTYYCVKFRKGSPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 9)

EEELQIIQPDKSVLVAAGETATLRCTITSLFPVGPIQWFRGAGPGRVLIYNQRDGPFPRVTTVSDGTKR

NNMDFSIRISSITPADVGTYYCVKFRKGTPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 10)

EEELQIIQPEKLLLVTVGKTATLHCTITSLFPVGPVLWFRGVGPGRVLIYNQRQGPFPRVTTVSDTTKR

NNMDFSIRISSITPADVGTYYCVKFRKGTPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 11)

EEELQIIQPEKLLLVTVGKTATLHCTITSLFPVGPIQWFRGVGPGRELIYNAREGRFPRVTTVSDLTKR

NNMDFSIRISSITPADVGTYYCVKFRKGSPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 12)

EEELQIIQPDKSVLVAAGETATLRCTITSLFPVGPIQWFRGAGPGRVLIYNQRQGPFPRVTTVSDTTKR

NNMDFSIRIGNITPADAGTYYCIKFRKGSPDDVEFKSGAGTELSVRAKPS;

(SEQ ID NO: 3)

EEELQIIQPEKLLLVTVGKTATLHCTITSLFPVGPVLWFRGVGPGRVLIYNQRQGPFPRVTTVSDTTKR

NNMDFSIRISSITPADVGTYYCIKFRKGSPENVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 13)

EEELQIIQPEKLLLVTVGKTATLHCTITSLFPVGPIQWFRGVGPGRVLIYNQREGPFPRVTTVSDGTKR

NNMDFSIRISSITPADVGTYYCVKFRKGSPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 42)

EEELQMIQPEKLLLVTVGKTATLHCTVTSLLPVGPVLWFRGVGPGRELIYNQKEGHFPRVTTVSDLT

KRNNMDFSIRISSITPADVGTYYCVKFRKGSPENVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 14)

EEELQIIQPDKSVLVAAGETATLRCTITSLFPVGPIQWFRGAGPGRVLIYNQRDGPFPRVTTVSDGTKR

NNMDFSIRISSITPADVGTYYCIKFRKGIPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 15)

EEELQIIQPDKSVLVAAGETATLRCTITSLFPVGPIQWFRGAGPGRVLIYNQRDGPFPRVTTVSDGTKR

NNMDFSIRISSITPADVGTYYCIKFRKGIPEDVEFKSGPGTXWH,

wherein X is A, R, N, D, C, Q, E, G, H, I, L, K, M, F. P, S, T, W, Y, or V;

(SEQ ID NO: 16)

EEELQIIQPDKSVLVAAGETATLRCTITSLFPVGPIQWFRGAGPGRVLIYNQKDGPFPRVTTVSDGTKR

NNMDFSIRISSITPADVGTYYCIKFRKGTPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 17)

EEELQIIQPEKLLLVTVGKTATLHCTITSLLPVGPIQWFRGVGPGRELIYNQRDGPFPRVTTVSDGTKR

NNMDFSIRISSITPADVGTYYCVKFRKGTPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 18)

EEELQIIQPEKLLLVTVGKTATLHCTLTSLLPVGPILWFRGVGPGRVLIYNQRDGPFPRVTTVSDGTKR

NNMDFSIRISSITPADVGTYYCVKFRKGNPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 19)

EEELQLIQPEKLLLVTVGKTATLHCTITSLFPPGPIQWFRGVGPGRVLIYNQKDGPFPRVTTVSDGTKR

NNMDFSIRISSITPADVGTYYCVKFRKGIPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 20)

EEELQIIQPEKLLLVTVGKTATLRCTITSLFPVGPIQWFRGAGPGRVLIYNQRDGPFPRVTTVSDGTKR

NNMDFSIRISSITPADVGTYYCIKFRKGIPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 21)

EEELQIIQPEKLLLVTVGKTATLHCTITSLFPIGPILWFRGVGPGRVLIYNQKDGPFPRVTTVSDGTKRN

NMDFSIRISSITPADVGTYYCVKFRKGSPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 22)

EEELQMIQPEKLLLVTVGKTATLHCTITSLFPVGPIQWFRGAGPGRVLIYNQRDGPFPRVTTVSDGTK

RNNMDFSIRISSITPADVGTYYCIKFRKGIPEDVEFKSGPGTEMALGAKPS.

15. The polypeptide of claim 1 , wherein the SIRP-gamma polypeptide is a fusion or chimeric polypeptide, and wherein the SIRP-gamma polypeptide is fused to a polypeptide sequence comprising an immune checkpoint inhibitor or a co-stimulatory molecule through a linker sequence.

16. The polypeptide of claim 15 , wherein the linker sequence comprises GGGGSGGGGS (SEQ ID NO: 29).

17. The polypeptide of claim 15 , wherein the SIRP-gamma polypeptide is located either N-terminal or C-terminal of the polypeptide sequence comprising an immune checkpoint inhibitor or co-stimulatory molecule.

18. The polypeptide of claim 15 , wherein the immune checkpoint inhibitor polypeptide comprises a sequence of a PD-1 or PD-L1 antagonist, a BTLA or CD160 antagonist, or a phosphatidylserine antagonist, e.g., MFGE8, TIM1, TIM3 or TIM4.

19. The polypeptide of claim 15 , wherein the co-stimulatory molecule polypeptide comprises a sequence of a CD40 agonist, a 41BBL or CD137 agonist.

20. The polypeptide of claim 15 , wherein the fusion or chimeric polypeptide comprises a sequence selected from:

(SEQ ID NO: 30)

DSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFHVVWHRESPSGQTDTLAAFPEDRSQPGQDA

RFRVTQLPNGRDFFIMSVVRARRNDSGTYVCGVISLAPKIQIKESLRAELRVTERGGGGSGGGGSEEE

LQIIQPEKLLLVTVGKTATLHCTITSLFPVGPIQWFRGVGPGRVLIYNQKDGHFPRVTTVSDGTKRNN

MDFSIRISSITPADVGTYYCVKFRKGSPEDVEFKSGPGTEMALGAKPS;

(SEQ ID NO: 31)