IP Library › Granted Patent US 11,746,139

Granted Patent B2

US 11,746,139 · App. 17/166,462 · Granted Sep 5, 2023

IL-7Rαγc binding compounds

Inventors: William J. Dower (Menlo Park, CA); Michael C. Needels (Menlo Park, CA); Ronald W. Barrett (Menlo Park, CA); Alice V. Bakker (Menlo Park, CA); Steven E. Cwirla (Menlo Park, CA)

Assignee: MEDIKINE, INC.

C07K14/7155 A61K38/00 C07K2319/00 C07K2319/30

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Quick Facts

Patent No.: US 11,746,139
App. No.: 17/166,462
Granted: Sep 5, 2023
Kind: B2

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Abstract

IL-7Rαγc binding compounds and pharmaceutical compositions comprising the IL-7Rαγc binding compounds are disclosed. IL-7Rαγc bonding compounds can act as IL-7R agonists and are useful in treating cancer, viral diseases, autoimmune diseases, and inflammatory diseases.

Claims (281)

1. An IL-7Rαγc ligand comprising:

(a) an IL-7Rα ligand, wherein,

the IL-7Rα ligand binds to the human IL-7Rα subunit with an IC 50 of less than 100 μM; and

the IL-7Rα ligand comprises an amino acid sequence selected from any one of SEQ ID NOS: 7, 15, 40, 60, 82, 87, 103, 115, 121, 177, 193, 210, 335, 381, 384, 402, 407, 582, and 655:

SEQ ID NO: 7

T C Q H Q D L Q G L L A C I

SEQ ID NO: 15

D W L C R P G P G L L V C Q W F

SEQ ID NO: 40

L Y C A E L H G F R V C R L

SEQ ID NO: 60

N I A C M R F P G G Y V C R N Y

SEQ ID NO: 82

V C R T T R L D N W W G C R

SEQ ID NO: 87

H C R L Q K P G F H R S S C

SEQ ID NO: 103

Y W A C S S G M N L C R W N

SEQ ID NO: 115

D C Y H W D L E S L L A C L

SEQ ID NO: 121

H C L H W D I E T L M S C V Y G N F E E

SEQ ID NO: 177

Y C M H W D L E S L L W C V H R K E L E

SEQ ID NO: 193

D R M V T G I P W C L L D P G S I Q C A W L

SEQ ID NO: 210

I P W C T L D P G S V Q C D Y L L K S A K Q

SEQ ID NO: 335

V P W C V L D P G S I Q C E Y L Q R L H R Q

SEQ ID NO: 381

R I E C A E L P G G F T C R L R

SEQ ID NO: 384

R Y E C A D L P G G L H C E F R

SEQ ID NO: 402

Q C V H W D L D T L F G C I R E Q L E L

SEQ ID NO: 407

V H R I P W C T L D P G G L Q C A W L R Q M

SEQ ID NO: 582

G G R S C L W Q P G A L H C T W W A E E E P V

SEQ ID NO: 655

G W G I P W C T L D P G S L Q C A W L G K H

(b) an Rγc ligand, wherein,

the Rγc ligand binds to the human Rγc subunit with an IC 50 of less than 100 μM; and

the Rγc ligand comprises an amino acid sequence selected from any one of SEQ ID NOS: 950 to 1028:

SEQ ID NO: 950

I E C D T S Y G V Y I C W Q

SEQ ID NO: 951

I E C E E W R G V E L C W Q

SEQ ID NO: 952

P E G R E V V V C R D W Y G V E L C W Q

SEQ ID NO: 953

I W G R T V V E C Q D W E G V E L C W Q

SEQ ID NO: 954

L A L R K E V V C Q E Y Y G V E L C W I

SEQ ID NO: 955

H E A R E V V V C Q D W Y G V E L C W Q

SEQ ID NO: 956

M V N R E V V V C E D W Y G V E L C W Q

SEQ ID NO: 957

T A N Q T V V E C Q V W G G V E L C W Q

SEQ ID NO: 958

V E C Q E W G G V E L C W C

SEQ ID NO: 959

D V E C V D W G G V E L C W H

SEQ ID NO: 960

I V C E E W R G V E L C W L

SEQ ID NO: 961

D F E R S Y V V C Q D W D G V E L C W I

SEQ ID NO: 962

A H S R Q E V V C E E W Y G V E L C W I

SEQ ID NO: 963

S A P E R W V E C E D W Q G V E L C W V

SEQ ID NO: 964

Y S R E L Y V Q C E D W E G V E L C W I

SEQ ID NO: 965

V V C Q D W E G V E L C W Q

SEQ ID NO: 966

D V V C Q N W E G V D L C W H

SEQ ID NO: 967

S A G R Q E V V C Q D W N G V E L C W I

SEQ ID NO: 968

G Q G R E V V V C H D W Y G V E L C W Q

SEQ ID NO: 969

D W R R S V V E C Q D W Y G V E L C W Q

SEQ ID NO: 970

D V V C Q N W D G V D L C W H

SEQ ID NO: 971

T L G R T V V E C Q D W G G V E L C W Q

SEQ ID NO: 972

R L L N S V V E C L D W E G V E L C W Q

SEQ ID NO: 973

I V C E D W R G V E L C W I

SEQ ID NO: 974

V V C Q E W E G V E L C W C

SEQ ID NO: 975

G D R P K E V V C E D W K G V E L C W I

SEQ ID NO: 976

E R P R S F I E C Q E W E G V E L C W L

SEQ ID NO: 977

E G S T T T I E C E E W A G V E L C W L

SEQ ID NO: 978

A N Q N T V V E C Q D W H G V E L C W Q

SEQ ID NO: 979

R S D D E V V V C Q E W E G V E L C W Q

SEQ ID NO: 980

I E C E E W A G V E L C W L

SEQ ID NO: 981

T W N M S E L E C Q D W N G V E I C W H

SEQ ID NO: 982

G N D D S Y I V C E E W K G V E L C W I

SEQ ID NO: 983

F A H H G V V E C Q E W Y G V E L C W Q

SEQ ID NO: 984

L N R S V W I E C E E Y E G V E L C W L

SEQ ID NO: 985

W S K K A E V V C E E W G G V E F C W I

SEQ ID NO: 986

R S N Q T V V E C Q D W E G V E L C W Q

SEQ ID NO: 987

V V C Q E W E G V E L C W Y A G E C M Q

SEQ ID NO: 988

I L C Q E F E G V E L C W L E E S L A E

SEQ ID NO: 989

K S Q V E C Q D W E G V E L C W V V S E

SEQ ID NO: 990

K I T V E C Q D W D G V E L C W P T W I

SEQ ID NO: 991

R P Q I E C Q E W Q G V E L C W T R E E

SEQ ID NO: 992

V S C Q E W D G V E L C W V D G D L A A

SEQ ID NO: 993

I M C Q E W D G V E L C W L E R D K A N

SEQ ID NO: 994

G L E I A C E D W Y G V E L C W L R R A

SEQ ID NO: 995

G Y G V L C Q E W Q G V E L C W P V Q R E A G V

SEQ ID NO: 996

P Y G V V C Q D W A G V E L C W V E N R

SEQ ID NO: 997

K L T V E C Q D W D G V E L C W V G V E

SEQ ID NO: 998

I N C Q T W N G V E L C W V D E G L Y Q

SEQ ID NO: 999

V V C Q E W E G V E L C W V E P P L L P

SEQ ID NO: 1000

R V Q V E C E D W N G V E L C W P V R V

SEQ ID NO: 1001

D R Q V V C E E W D G V E L C W I E E S

SEQ ID NO: 1002

K T T V A C Q D W G G V E L C W V E R V

SEQ ID NO: 1003

R P E V V C Q E W E G V E L C W I S P L

SEQ ID NO: 1004

R L G V E C Q E W E G V D L C W I S A F

SEQ ID NO: 1005

K P V V V C E E W Q G V E L C W L E I Q

SEQ ID NO: 1006

V V C E V F Q G V E L C W C E N E E F T

SEQ ID NO: 1007

T D E V S C Q E W E G V E L C W I E R Q

SEQ ID NO: 1008

P V E V R C Q E W E G V E L C W V V G I

SEQ ID NO: 1009

G P E V V C E E F N R V E L C W V E Y N

SEQ ID NO: 1010

K Y I V E C Q E W G G V E L C W P E M V

SEQ ID NO: 1011

V T C Q E Y E G V E L C W T V G C A Y S

SEQ ID NO: 1012

V V C Q E W E G V E L C W Q T G P G A H A

SEQ ID NO: 1013

I V C E E Y N G V E L C W V E T S V K P

SEQ ID NO: 1014

E Q Q V V C Q E W N G V E L C W I E A G

SEQ ID NO: 1015

Q L G V E C Q N W R G V E L C W V S E I

SEQ ID NO: 1016

T A E V V C Q E W D G V E L C W I E V L

SEQ ID NO: 1017

S P S I V C E E W A G V E L C W V D Y S

SEQ ID NO: 1018

A V C Q D W Y G V E L C W C M Q D I L D

SEQ ID NO: 1019

V E C E E W G G V E L C W L A D E V M W

SEQ ID NO: 1020

H S T V I C Q D W D G V E L C W I E N D

SEQ ID NO: 1021

K K I V V C Q D W G G V E L C W T E D D

SEQ ID NO: 1022

S V E V V C E E W H G V E L C W P V F I

SEQ ID NO: 1023

R W A V S C Q D W Q G I E L C W P E W D

SEQ ID NO: 1024

R T G V E C Q D W H G V E L C W P V W E

SEQ ID NO: 1025

G Y G V V C E D F R G V E L C W L E R K

SEQ ID NO: 1026

R T E V E C E D W E G V E L C W L

SEQ ID NO: 1027

I L C E E W Q G V E L C W L E G G G S

SEQ ID NO: 1028

V G I E C E E W A G V E L C W L

and,

2. The IL-7Rαγc ligand of claim 1 , wherein the linker comprises a peptide linker.

3. The IL-7Rαγc ligand of claim 2 , wherein the peptide linker is selected from (G)n (SEQ ID NO: 9390), (GS)n (SEQ ID NO: 9391), (GGS)n (SEQ ID NO: 9392), (GGGS)n (SEQ ID NO: 9393), (GGGGS)n (SEQ ID NO: 9394) or a combination of any of the foregoing, where n is an integer from 1 to 5.

4. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rαγc ligand binds to the human IL-7Rα subunit with an IC 50 less than 100 μM; and to the human Rγc subunit with an IC 50 less than 100 μM.

5. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rγc ligand exhibits an EC 50 for STAT5 phosphorylation in TF-1-7α cells of less than 1E10-7 M.

6. A compound comprising the IL-7Rαγc ligand of claim 1 .

7. The compound of claim 6 , wherein the compound comprises the IL-7Rαγc ligand bound to a construct partner through a construct linker.

8. The compound of claim 7 , wherein the construct linker is selected from ((G) n (SEQ ID NO: 9380), (GS) n (SEQ ID NO: 9381), (GGS) n (SEQ ID NO: 9382), (GGGS) n (SEQ ID NO: 9383), (GGGGS) n (SEQ ID NO: 9384) or a combination of any of the foregoing, where n is an integer from 1 to 20.

9. The compound of claim 6 , wherein the construct partner comprises a protein.

10. The compound of claim 7 , wherein the construct partner comprises an Fc fragment.

11. A pharmaceutical composition comprising the IL-7Rαγc ligand of claim 1 .

12. A pharmaceutical composition comprising the compound of claim 6 .

13. An IL-7Rαγc ligand comprising any one of SEQ ID NO: 2012, 2060, 2063, 2068, 2069, 2084-2087, 2089, and 2095:

SEQ ID NO: 2012

VHRIPWCTLDPGGLQCAWLRQMGGGGSGGVVCQDWEGVELCWQ

SEQ ID NO: 2060

VHRIPWCTLDPGGLQCAWLRQMGGGGSGGVVCQDWEGVELCWQPPA

SEQ ID NO: 2063

GWGIPWCTLDPGSLQCAWLGKHGGGGSGGVVCQDWEGVELCWQPPA

SEQ ID NO: 2068

GWGIPWCTLDPGSLQCAWLGKHGGGGSGGVVCQDWEGVELCWQGG

SEQ ID NO: 2069

VHRIPWCTLDPGGLQCAWLRQM(PA) 8 GVVCQDWEGVELCWQGG

SEQ ID NO: 2084

VHRIPWCTLDPGGLQCAWLRQMGGGGSGGVVCQDWEGVELCWQG

SEQ ID NO: 2085

VHRIPWCTLDPGGLQCAWLRQMGGGGSGGVVCQDWEGVELCWQGG

SEQ ID NO: 2086

GVHRIPWCTLDPGGLQCAWLRQMGGGGSGGVVCQDWEGVELCWQGG

SEQ ID NO: 2087

GGVHRIPWCTLDPGGLQCAWLRQMGGGGSGGVVCQDWEGVELCWQGG

SEQ ID NO: 2089

WGIPWCTLDPGSLQCAWLGKHGGGGSGGVVCQDWEGVELCWQ

SEQ ID NO: 2095

GVHRIPWCTLDPGGLQCAWLRQMGGGGSGGVVCQDWEGVELCWQG

or greater than 60% sequence similarity to any one of SEQ ID NO: 2012, 2060, 2063, 2068, 2069, 2084-2087, 2089, and 2095.

14. The IL-7Rαγc ligand of claim 13 , wherein the IL-7Rαγc ligand has greater than 60% sequence similarity to any one of SEQ ID NO: 2012, 2060, 2063, 2068, 2069, 2084-2087, 2089, and 2095.

15. The IL-7Rαγc ligand of claim 13 , wherein the IL-7Rαγc ligand comprises SEQ ID NO: 2012.

16. The IL-7Rαγc ligand of claim 13 , wherein the IL-7Rαγc ligand has greater than 60% sequence similarity to SEQ ID NO: 2012.

17. The IL-7Rαγc ligand of claim 13 , wherein the IL-7Rαγc ligand comprises SEQ ID NO: 2068.

18. The IL-7Rαγc ligand of claim 13 , wherein the IL-7Rαγc ligand has greater than 60% sequence similarity to SEQ ID NO: 2068.

19. An IL-7Rαγc ligand comprising:

(a) an IL-7Rα ligand, wherein,

the IL-7Rα ligand binds to the human IL-7Rα subunit with an IC 50 of less than 100 μM; and

the IL-7Rα ligand comprises greater than 60% sequence similarity to any one of SEQ ID NO: 407, 454-469, 655, and 530-556:

b) an Rγc ligand, wherein,

the Rγc ligand binds to the human Rγc subunit with an IC 50 of less than 100 μM; and

the Rγc ligand comprises greater than 60% sequence similarity to any one of SEQ ID NO: 950 to 1028; and,

20. The IL-7Rαγc ligand of claim 19 , wherein the Rγc ligand has greater than 60% sequence similarity to any one of SEQ ID NO: 950 to 1028.

21. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rα ligand comprises any one of SEQ ID NO: 407 and SEQ ID NO: 655.

22. The IL-7Rαγc ligand of claim 19 , wherein the IL-7Rα ligand comprises an amino acid sequence having greater than 60% sequence similarity to any one of SEQ ID NO: 407 and SEQ ID NO: 655.

23. The IL-7Rαγc ligand of claim 1 , wherein the Rγc ligand comprises SEQ ID NO: 965.

24. The IL-7Rαγc ligand of claim 19 , wherein the Rγc ligand comprises an amino acid sequence having greater than 60% sequence similarity to SEQ ID NO: 965.

25. The IL-7Rαγc ligand of claim 1 , wherein,

the IL-7Rα ligand comprises any one of SEQ ID NO: 407 and SEQ ID NO: 655; and

the Rγc ligand comprises SEQ ID NO: 965.

26. The IL-7Rαγc ligand of claim 19 , wherein,

the IL-7Rα ligand comprises an amino acid sequence having greater than 60% sequence similarity to any one of SEQ ID NO: 407 and SEQ ID NO: 655; and

the Rγc ligand comprises an amino acid sequence having greater than 60% sequence similarity to any one of SEQ ID NO: 965.

27. The IL-7Rαγc ligand of claim 13 , wherein the IL-7Rαγc ligand comprises SEQ ID NO: 2086.

28. The IL-7Rαγc ligand of claim 13 , wherein the IL-7Rαγc ligand has greater than 60% sequence similarity to SEQ ID NO: 2086.

29. The IL-7Rαγc ligand of claim 13 , wherein the IL-7Rαγc ligand comprises SEQ ID NO: 2089.

30. The IL-7Rαγc ligand of claim 13 , wherein the IL-7Rαγc ligand has greater than 60% sequence similarity to SEQ ID NO: 2089.

31. The IL-7Rαγc ligand of claim 19 , wherein the linker is selected from (G)n (SEQ ID NO: 9390), (GS)n (SEQ ID NO: 9391), (GGS)n (SEQ ID NO: 9392), (GGGS)n (SEQ ID NO: 9393), (GGGGS)n (SEQ ID NO: 9394) or a combination of any of the foregoing, where n is an integer from 1 to 5.

32. The IL-7Rαγc ligand of claim 19 , wherein the linker is GGGGSGG.

33. The IL-7Rαγc ligand of claim 19 , wherein the linker is selected from (P) n (SEQ ID NO: 9420), (PA) n (SEQ ID NO: 9421), (PA) 5 (SEQ ID NO: 9426), (PA) 7 (SEQ ID NO: 9427) or (PA) 10 (SEQ ID NO: 9428), wherein n is an integer from 1 to 20.

34. The IL-7Rαγc ligand of claim 1 wherein the linker is selected from (P) n (SEQ ID NO: 9420), (PA) n (SEQ ID NO: 9421), (PA) 5 (SEQ ID NO: 9426), (PA) 7 (SEQ ID NO: 9427) or (PA) 10 (SEQ ID NO: 9428), wherein n is an integer from 1 to 20.

35. The IL-7Rαγc ligand of claim 19 , wherein,

the IL-7Rα ligand comprises any one of SEQ ID NO: 407, 454-469, 655, and 530-556; and

the Rγc ligand comprises any one of SEQ ID NO: 950 to 1028.

36. The IL-7Rαγc ligand of claim 19 , wherein,

the IL-7Rα ligand comprises any one of SEQ ID NO: 407 and 454-469; and

the Rγc ligand comprises SEQ ID NO: 965.

37. The IL-7Rαγc ligand of claim 19 , wherein,

the IL-7Rα ligand comprises any one of SEQ ID NO: 655 and 530-556; and

the Rγc ligand comprises SEQ ID NO: 965.

Assignments (2)

SECURITY INTEREST Recorded Oct 20, 2023

From: MEDIKINE, INC.

To: SAMSARA BIOCAPITAL, L.P.; LIGHTSPEED GENERAL PARTNER XIV-B (IGNITE), L.P.; BLUEBIRD VENTURES I, L.P.; JEFFREY W. AND CHRISTINA R. BIRD TRUST U/A/D; MCMEEKIN, DERMOT; WS INVESTMENT COMPANY, LLC (23A)

Reel/Frame 065303/0643 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 23, 2021

From: DOWER, WILLIAM J.; NEEDELS, MICHAEL C.; BARRETT, RONALD W.; BAKKER, ALICE V.; CWIRLA, STEVEN E.

To: MEDIKINE, INC.

Reel/Frame 055374/0799 →

Continuity (3)

Provisional Application 63041158 · Jun 19, 2020

Provisional Application 62969432 · Feb 3, 2020

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