CO-CRYSTALS OF A BRUTON'S TYROSINE KINASE INHIBITOR

1 . A co-crystal of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one and a coformer.

2 . The co-crystal of claim 1 , wherein the coformer is benzoic acid, succinic acid, 3-hydroxybenzoic acid, nicotinamide, 4-aminobenzoic acid, salicylic acid, sorbic acid, fumaric acid, salicylamide, trans-cinnamic acid, 4-hydroxybenzoic acid, 1-hydroxy-2-naphthoic acid, sulfamic acid, 1,5-naphthalene disulfonic acid, 2-ethoxybenzamide, 4-aminosalicylic acid, or stearic acid, or a combination thereof.

3 . A co-crystal of benzoic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two, four, or all of the characteristic peaks at 9.0±0.1° 2-Theta, 12.1±0.1° 2-Theta, 18.2±0.1° 2-Theta, 21.2±0.1° 2-Theta, 22.9±0.1° 2-Theta, and 27.9±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(d) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 25° C. and 97% RH for at least a week;

(e) a DSC thermogram substantially the same as the one set forth in FIG. 2 ;

(f) a DSC thermogram with an endotherm having an onset at about 131° C. and a peak at about 134° C.;

(g) a thermo-gravimetric analysis (TGA) thermogram substantially the same as the one set forth in FIG. 2 ;

(h) unit cell parameters approximately equal to the following at a temperature of approximately 100(2) K:

Molecular formula

C 32 H 30 N 6 O 4

Molecular weight

562.62

Crystal system

Triclinic

Space group

P1

a

7.3655(4) Å

α

82.759(4)°

b

9.7471(5) Å

β

81.994(4)°

c

9.8571(5) Å

γ

87.851(4)°

V

695.03(6) Å 3

Z

1

Density (calculated)

1.344 Mg/m 3

Absorption coefficient

0.741 mm −1

Wavelength

1.54178 Å

F(000)

296

T

100(2) K

or

(i) combinations thereof.

4 . The co-crystal of claim 3 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1 .

5 . The co-crystal of claim 3 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 9.0±0.1° 2-Theta, 12.1±0.1° 2-Theta, 18.2±0.1° 2-Theta, 21.2±0.1° 2-Theta, 22.9±0.1° 2-Theta, and 27.9±0.1° 2-Theta.

6 . The co-crystal of claim 3 , wherein the co-crystal has substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week.

7 . The co-crystal of claim 3 , wherein the co-crystal has substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 25° C. and 97% RH for at least a week.

8 . The co-crystal of claim 3 , wherein the co-crystal has a DSC thermogram substantially the same as the one set forth in FIG. 2 .

9 . The co-crystal of claim 3 , wherein the DSC thermogram has an endotherm having an onset at about 131° C. and a peak at about 134° C.

10 . The co-crystal of claim 3 , wherein the co-crystal has a TGA thermogram substantially the same as the one set forth in FIG. 2 .

11 . The co-crystal of claim 3 , wherein the unit cell parameters approximately equal to the following at a temperature of approximately 100(2) K:

Molecular formula

C 32 H 30 N 6 O 4

Molecular weight

562.62

Crystal system

Triclinic

Space group

P1

a

7.3655(4) Å

α

82.759(4)°

b

9.7471(5) Å

β

81.994(4)°

c

9.8571(5) Å

γ

87.851(4)°

V

695.03(6) Å 3

Z

1

Density (calculated)

1.344 Mg/m 3

Absorption coefficient

0.741 mm −1

Wavelength

1.54178 Å

F(000)

296

T

100(2) K

12 . The co-crystal of claim 3 , wherein the co-crystal is characterized as having properties (a), (b), (c), (d), (e), (f), (g), and (h).

13 . A co-crystal of succinic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 3 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two, four, six, or all of the characteristic peaks at 17.3±0.1° 2-Theta, 18.0±0.1° 2-Theta, 18.3±0.1° 2-Theta, 20.1±0.1° 2-Theta, 20.3±0.1° 2-Theta, 21.6±0.1° 2-Theta, 21.8±0.1° 2-Theta, 23.2±0.1° 2-Theta, 24.2±0.1° 2-Theta, and 26.2±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(d) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 25° C. and 97% RH for at least a week;

(e) a DSC thermogram substantially the same as the one set forth in FIG. 4 ;

(f) a DSC thermogram with an endotherm having an onset at about 128° C. and a peak at about 131° C.;

(g) thermo-gravimetric analysis (TGA) thermogram substantially the same as the one set forth in FIG. 4 ;

or

(h) combinations thereof.

14 . The co-crystal of claim 13 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 3 .

15 . The co-crystal of claim 13 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 17.3±0.1° 2-Theta, 18.0±0.1° 2-Theta, 18.3±0.1° 2-Theta, 20.1±0.1° 2-Theta, 20.3±0.1° 2-Theta, 21.6±0.1° 2-Theta, 21.8±0.1° 2-Theta, 23.2±0.1° 2-Theta, 24.2±0.1° 2-Theta, and 26.2±0.1° 2-Theta.

16 . The co-crystal of claim 13 , wherein the co-crystal has substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week.

17 . The co-crystal of claim 13 , wherein the co-crystal has substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 25° C. and 97% RH for at least a week.

18 . The co-crystal of claim 13 , wherein the co-crystal has a DSC thermogram substantially the same as the one set forth in FIG. 4 .

19 . The co-crystal of claim 13 , wherein the DSC thermogram with an endotherm having an onset at about 128° C. and a peak at about 131° C.

20 . The co-crystal of claim 13 , wherein the co-crystal has a TGA thermogram substantially the same as the one set forth in FIG. 4 .

21 . The co-crystal of claim 13 , wherein the co-crystal is characterized as having properties (a), (b), (c), (d), (e), (f), and (g).

22 . A co-crystal of 3-hydroxybenzoic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 5 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two, four, six, or all of the characteristic peaks at 12.5±0.1° 2-Theta, 14.8±0.1° 2-Theta, 18.0±0.1° 2-Theta, 18.9±0.1° 2-Theta, 20.3±0.1° 2-Theta, 22.8±0.1° 2-Theta, and 23.8±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(d) a DSC thermogram substantially the same as the one set forth in FIG. 6 ;

(e) a DSC thermogram with an endotherm having an onset at about 127° C. and a peak at about 132° C.;

or

(f) combinations thereof.

23 . The co-crystal of claim 22 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 5 .

24 . The co-crystal of claim 22 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 12.5±0.1° 2-Theta, 14.8±0.1° 2-Theta, 18.0±0.1° 2-Theta, 18.9±0.1° 2-Theta, 20.3±0.1° 2-Theta, 22.8±0.1° 2-Theta, and 23.8±0.1° 2-Theta.

25 . The co-crystal of claim 22 , wherein the co-crystal has substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week.

26 . The co-crystal of claim 22 , wherein the co-crystal has a DSC thermogram substantially the same as the one set forth in FIG. 6 .

27 . The co-crystal of claim 22 , wherein the DSC thermogram with an endotherm having an onset at about 127° C. and a peak at about 132° C.

28 . The co-crystal of claim 22 , wherein the co-crystal is characterized as having properties (a), (b), (c), (d), and (e).

29 . A co-crystal of nicotinamide and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 7 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two, four, six, or all of the characteristic peaks at 5.4±0.1° 2-Theta, 14.8±0.1° 2-Theta, 15.8±0.1° 2-Theta, 18.3±0.1° 2-Theta, 19.1±0.1° 2-Theta, 19.7±0.1° 2-Theta, 21.3±0.1° 2-Theta, 21.8±0.1° 2-Theta, 25.9±0.1° 2-Theta, and 27.3±0.1° 2-Theta;

(c) a DSC thermogram substantially the same as the one set forth in FIG. 8 ;

(d) a DSC thermogram with an endotherm having an onset at about 104° C. and a peak at about 113° C.;

or

(e) combinations thereof.

30 . The co-crystal of claim 29 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 7 .

31 . The co-crystal of claim 29 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 5.4±0.1° 2-Theta, 14.8±0.1° 2-Theta, 15.8±0.1° 2-Theta, 18.3±0.1° 2-Theta, 19.1±0.1° 2-Theta, 19.7±0.1° 2-Theta, 21.3±0.1° 2-Theta, 21.8±0.1° 2-Theta, 25.9±0.1° 2-Theta, and 27.3±0.1° 2-Theta.

32 . The co-crystal of claim 29 , wherein the co-crystal has a DSC thermogram substantially the same as the one set forth in FIG. 8 .

33 . The co-crystal of claim 29 , wherein the DSC thermogram with an endotherm having an onset at about 104° C. and a peak at about 113° C.

34 . The co-crystal of claim 29 , wherein the co-crystal is characterized as having properties (a), (b), (c), and (d).

35 . A co-crystal of 4-aminobenzoic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 9 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two, four, six, or all of the characteristic peaks at 5.8±0.1° 2-Theta, 6.6±0.1° 2-Theta, 13.1±0.1° 2-Theta, 17.7±0.1° 2-Theta, 18.2±0.1° 2-Theta, 20.2±0.1° 2-Theta, 21.2±0.1° 2-Theta, 21.3±0.1° 2-Theta, 21.6±0.1° 2-Theta, and 22.4±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(d) a DSC thermogram substantially the same as the one set forth in FIG. 10 ;

(e) a DSC thermogram with an endotherm having an onset at about 128° C. and a peak at about 132° C.;

or

(f) combinations thereof.

36 . The co-crystal of claim 35 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 9 .

37 . The co-crystal of claim 35 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 5.8±0.1° 2-Theta, 6.6±0.1° 2-Theta, 13.1±0.1° 2-Theta, 17.7±0.1° 2-Theta, 18.2±0.1° 2-Theta, 20.2±0.1° 2-Theta, 21.2±0.1° 2-Theta, 21.3±0.1° 2-Theta, 21.6±0.1° 2-Theta, and 22.4±0.1° 2-Theta.

38 . The co-crystal of claim 35 , wherein the co-crystal has substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week.

39 . The co-crystal of claim 35 , wherein the co-crystal has a DSC thermogram substantially the same as the one set forth in FIG. 10 .

40 . The co-crystal of claim 35 , wherein the DSC thermogram with an endotherm having an onset at about 128° C. and a peak at about 132° C.

41 . The co-crystal of claim 35 , wherein the co-crystal is characterized as having properties (a), (b), (c), (d), and (e).

42 . A co-crystal of salicylic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 11 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two, four, six, or all of the characteristic peaks at 12.6±0.1° 2-Theta, 14.8±0.1° 2-Theta, 18.0±0.1° 2-Theta, 19.0±0.1° 2-Theta, 19.8±0.1° 2-Theta, 20.2±0.1° 2-Theta, and 22.9±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(d) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 25° C. and 97% RH for at least a week;

(e) a DSC thermogram substantially the same as the one set forth in FIG. 12 ;

(f) a DSC thermogram with an endotherm having an onset at about 131° C. and a peak at about 134° C.;

(g) thermo-gravimetric analysis (TGA) thermogram substantially the same as the one set forth in FIG. 12 ;

or

(h) combinations thereof.

43 . The co-crystal of claim 42 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 11 .

44 . The co-crystal of claim 42 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 12.6±0.1° 2-Theta, 14.8±0.1° 2-Theta, 18.0±0.1° 2-Theta, 19.0±0.1° 2-Theta, 19.8±0.1° 2-Theta, 20.2±0.1° 2-Theta, and 22.9±0.1° 2-Theta.

45 . The co-crystal of claim 42 , wherein the co-crystal has substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week.

46 . The co-crystal of claim 42 , wherein the co-crystal has substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 25° C. and 97% RH for at least a week.

47 . The co-crystal of claim 42 , wherein the co-crystal has a DSC thermogram substantially the same as the one set forth in FIG. 12 .

48 . The co-crystal of claim 42 , wherein the DSC thermogram with an endotherm having an onset at about 131° C. and a peak at about 134° C.

49 . The co-crystal of claim 42 , wherein the co-crystal has a TGA thermogram substantially the same as the one set forth in FIG. 12 .

50 . The co-crystal of claim 42 , wherein the co-crystal is characterized as having properties (a), (b), (c), (d), (e), (f), and (g).

51 . A co-crystal of sorbic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 13 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two, four, six, or all of the characteristic peaks at 5.5±0.1° 2-Theta, 16.4±0.1° 2-Theta, 18.5±0.1° 2-Theta, 19.0±0.1° 2-Theta, 21.1±0.1° 2-Theta, 21.6±0.1° 2-Theta, 22.8±0.1° 2-Theta, and 24.8±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(d) a DSC thermogram substantially the same as the one set forth in FIG. 14 ;

(e) a DSC thermogram with an endotherm having an onset at about 79° C. and a peak at about 98° C.;

or

(f) combinations thereof.

52 . The co-crystal of claim 51 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 13 .

53 . The co-crystal of claim 51 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 5.5±0.1° 2-Theta, 16.4±0.1° 2-Theta, 18.5±0.1° 2-Theta, 19.0±0.1° 2-Theta, 21.1±0.1° 2-Theta, 21.6±0.1°2-Theta, 22.8±0.1° 2-Theta, and 24.8±0.1° 2-Theta.

54 . The co-crystal of claim 51 , wherein the co-crystal has substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week.

55 . The co-crystal of claim 51 , wherein the co-crystal has a DSC thermogram substantially the same as the one set forth in FIG. 14 .

56 . The co-crystal of claim 51 , wherein the DSC thermogram with an endotherm having an onset at about 79° C. and a peak at about 98° C.

57 . The co-crystal of claim 51 , wherein the co-crystal is characterized as having properties (a), (b), (c), (d), and (e).

58 . A co-crystal of fumaric acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 15 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two, four, six, or all of the characteristic peaks at 9.9±0.1° 2-Theta, 10.8±0.1° 2-Theta, 17.4±0.1° 2-Theta, 18.2±0.1° 2-Theta, 20.5±0.1° 2-Theta, 21.7±0.1° 2-Theta, 23.9±0.1° 2-Theta, 24.6±0.1° 2-Theta, and 28.9±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(d) a DSC thermogram substantially the same as the one set forth in FIG. 16 ;

(e) a DSC thermogram with a sharp endotherm onset at about 145° C. and a peak at about 149° C.;

or

(f) combinations thereof.

59 . The co-crystal of claim 58 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 15 .

60 . The co-crystal of claim 58 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 9.9±0.1° 2-Theta, 10.8±0.1° 2-Theta, 17.4±0.1° 2-Theta, 18.2±0.1° 2-Theta, 20.5±0.1° 2-Theta, 21.7±0.1° 2-Theta, 23.9±0.1 2-Theta, 24.6±0.1° 2-Theta, and 28.9±0.1° 2-Theta.

61 . A co-crystal of salicylamide and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 17 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two, four, six, or all of the characteristic peaks at 5.3±0.1° 2-Theta, 8.5±0.1° 2-Theta, 13.1±0.1° 2-Theta, 15.8±0.1° 2-Theta, 16.4±0.1° 2-Theta, 16.9±0.1° 2-Theta, 18.4±0.1° 2-Theta, 19.0±0.1° 2-Theta, 21.2±0.1° 2-Theta, and 21.7±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(d) a DSC thermogram substantially the same as the one set forth in FIG. 18 ;

(e) a DSC thermogram with an endotherm having a broad endotherm at about 101° C. and a peak at about 107° C.;

or

(f) combinations thereof.

62 . The co-crystal of claim 61 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 17 .

63 . The co-crystal of claim 61 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks 5.3±0.1° 2-Theta, 8.5±0.1° 2-Theta, 13.1±0.1° 2-Theta, 15.8±0.1° 2-Theta, 16.4±0.1° 2-Theta, 16.9±0.1° 2-Theta, 18.4±0.1° 2-Theta, 19.0±0.1° 2-Theta, 21.2±0.1° 2-Theta, and 21.7±0.1° 2-Theta.

64 . A co-crystal Form 1 of trans-cinnamic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 19 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two of the characteristic peaks at 5.7±0.1° 2-Theta, 6.4±0.1° 2-Theta, 9.8±0.1° 2-Theta, 10.2±0.1° 2-Theta, 12.8±0.1° 2-Theta, 18.6±0.1° 2-Theta, 19.4±0.1° 2-Theta, 20.5±0.1° 2-Theta, 21.9±0.1° 2-Theta, 22.1±0.1° 2-Theta, and 23.0±0.1° 2-Theta;

(c) a DSC thermogram substantially the same as the one set forth in FIG. 20 ;

(d) a DSC thermogram with two endotherms; one with an onset at about 97° C. and a peak at about 101° C., and a second with an onset at about 140° C. and a peak at about 146° C.;

or

(e) combinations thereof.

65 . The co-crystal of claim 64 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 19 .

66 . The co-crystal of claim 51 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 5.7±0.1° 2-Theta, 6.4±0.1° 2-Theta, 9.8±0.1° 2-Theta, 10.2±0.1° 2-Theta, 12.8±0.1° 2-Theta, 18.6±0.1° 2-Theta, 19.4±0.1° 2-Theta, 20.5±0.1° 2-Theta, 21.9±0.1° 2-Theta, 22.1±0.1° 2-Theta, and 23.0±0.1° 2-Theta.

67 . A co-crystal of 4-hydroxybenzoic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 21 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two of the characteristic peaks at 6.6±0.1° 2-Theta, 6.9±0.1° 2-Theta, 13.6±0.1° 2-Theta, 17.3±0.1° 2-Theta, 18.4±0.1° 2-Theta, 19.0±0.1° 2-Theta, 20.7±0.1° 2-Theta, 23.6±0.1° 2-Theta, 24.1±0.1° 2-Theta, and 25.0±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(d) a DSC thermogram substantially the same as the one set forth in FIG. 22 ;

(e) a DSC thermogram with a broad endotherm with an onset at about 69° C. and a peak at about 99° C., followed by an exotherm with an onset at about 125° C. and a peak at about 146° C., and a second endotherm with an onset at about 219° C. and a peak at about 235° C.;

or

(f) combinations thereof.

68 . The co-crystal of claim 67 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 21 .

69 . The co-crystal of claim 51 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 6.6±0.1° 2-Theta, 6.9±0.1° 2-Theta, 13.6±0.1° 2-Theta, 17.3±0.1° 2-Theta, 18.4±0.1° 2-Theta, 19.0±0.1° 2-Theta, 20.7±0.1° 2-Theta, 23.6±0.1° 2-Theta, 24.1±0.1° 2-Theta, and 25.0±0.1° 2-Theta.

70 . A co-crystal of 1-hydroxy-2-naphthoic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 23 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two of the characteristic peaks at 6.7±0.1° 2-Theta, 13.6±0.1° 2-Theta, 14.8±0.1° 2-Theta, 18.9±0.1° 2-Theta, 20.4±0.1° 2-Theta, 21.6±0.1° 2-Theta, 23.6±0.1° 2-Theta, and 26.6±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(d) a DSC thermogram substantially the same as the one set forth in FIG. 24 ;

(e) a DSC thermogram with two endotherms; one with an onset at about 137° C. and a peak at about 142° C. and a second with an onset at about 163° C. and a peak at about 170° C.;

or

(f) combinations thereof.

71 . The co-crystal of claim 70 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 23 .

72 . The co-crystal of claim 70 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 6.7±0.1° 2-Theta, 13.6±0.1° 2-Theta, 14.8±0.1° 2-Theta, 18.9±0.1° 2-Theta, 20.4±0.1° 2-Theta, 21.6±0.1° 2-Theta, 23.6±0.1° 2-Theta, and 26.6±0.1° 2-Theta.

73 . A co-crystal of sulfamic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 25 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two of the characteristic peaks at 6.9±0.1° 2-Theta, 17.3±0.1° 2-Theta, 20.4±0.1° 2-Theta, 20.6±0.1° 2-Theta, 20.8±0.1° 2-Theta, 22.3±0.1° 2-Theta, 23.0±0.1° 2-Theta, and 27.0±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(d) a DSC thermogram substantially the same as the one set forth in FIG. 26 ;

(e) a DSC thermogram with a broad endotherm with an onset at about 153° C. and a peak at about 171° C.;

or

(f) combinations thereof.

74 . The co-crystal of claim 73 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 25 .

75 . The co-crystal of claim 73 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 6.9±0.1° 2-Theta, 17.3±0.1° 2-Theta, 20.4±0.1° 2-Theta, 20.6±0.1° 2-Theta, 20.8±0.1° 2-Theta, 22.3±0.1° 2-Theta, 23.0±0.1° 2-Theta, and 27.0±0.1° 2-Theta.

76 . A co-crystal of 1,5-naphthalene disulfonic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 27 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two of the characteristic peaks at 4.4±0.1° 2-Theta, 6.9±0.1° 2-Theta, 17.0±0.1° 2-Theta, 17.4±0.1° 2-Theta, 20.0±0.1° 2-Theta, 20.5±0.1° 2-Theta, and 23.1±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week

(d) a DSC thermogram substantially the same as the one set forth in FIG. 28 ;

(e) a DSC thermogram with three broad endotherms; one with an onset at about 42° C. and a peak at about 53° C., followed by one with an onset at about 89° C. and a peak at about 109° C., and one with an onset at about 165° C. with a peak at about 178° C.;

or

(f) combinations thereof.

77 . The co-crystal of claim 76 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 27 .

78 . The co-crystal of claim 76 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 4.4±0.1° 2-Theta, 6.9±0.1° 2-Theta, 17.0±0.1° 2-Theta, 17.4±0.1° 2-Theta, 20.0±0.1° 2-Theta, 20.5±0.1° 2-Theta, and 23.1±0.1° 2-Theta.

79 . A co-crystal of 2-ethoxybenzamide and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern with at least two of the characteristic peaks at 5.4±0.1° 2-Theta, 5.8±0.1° 2-Theta, and 19.8±0.1° 2-Theta;

(b) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(c) a DSC thermogram substantially the same as the one set forth in FIG. 30 ;

(d) a DSC thermogram with a small endotherm with an onset at about 70° C. and a peak at about 85° C., a sharp endotherm with an onset at about 109° C. with a peak at about 114° C., and two broad endotherms between about 120-135° C.;

(e) thermo-gravimetric analysis (TGA) thermogram substantially the same as the one set forth in FIG. 30 ;

or

(f) combinations thereof.

80 . The co-crystal of claim 79 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 29 .

81 . The co-crystal of claim 79 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 5.4±0.1° 2-Theta, 5.8±0.1° 2-Theta, and 19.8±0.1° 2-Theta.

82 . A co-crystal of 4-aminosalicylic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 31 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two of the characteristic peaks at 6.0±0.1° 2-Theta, 6.4±0.1° 2-Theta, 13.1±0.1° 2-Theta, 13.2±0.1° 2-Theta, 14.0±0.1° 2-Theta, 21.9±0.1° 2-Theta, and 24.0±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week;

(d) a DSC thermogram substantially the same as the one set forth in FIG. 32 ;

(e) a DSC thermogram with two broad endotherms; one with an onset at about 80° C. and a peak at about 93° C., and one with an onset about 138° C. and a peak at about 155° C.;

or

(f) combinations thereof.

83 . The co-crystal of claim 82 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 31 .

84 . The co-crystal of claim 82 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 6.0±0.1° 2-Theta, 6.4±0.1° 2-Theta, 13.1±0.1° 2-Theta, 13.2±0.1° 2-Theta, 14.0±0.1° 2-Theta, 21.9±0.1° 2-Theta, and 24.0±0.1° 2-Theta.

85 . A co-crystal of stearic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 33 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two of the characteristic peaks at 3.2±0.1° 2-Theta, 9.5±0.1° 2-Theta, 20.6±0.1° 2-Theta, 21.7±0.1° 2-Theta, 22.9±0.1° 2-Theta, and 23.2±0.1° 2-Theta;

(c) a DSC thermogram substantially the same as the one set forth in FIG. 34 ;

(d) a DSC thermogram with two sharp endotherms; one with an onset at about 67° C. and a peak at about 69° C., and one with an onset at about 94° C. and a peak at about 96° C., followed by a small endotherm with an onset at about 119° C. and a peak at about 124° C.;

or

(e) combinations thereof.

86 . The co-crystal of claim 85 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 33 .

87 . The co-crystal of claim 85 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 3.2±0.1° 2-Theta, 9.5±0.1° 2-Theta, 20.6±0.1° 2-Theta, 21.7±0.1° 2-Theta, 22.9±0.1° 2-Theta, and 23.2±0.1° 2-Theta.

88 . A co-crystal Form 2 of trans-cinnamic acid and 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has at least one of the following properties:

(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 35 ;

(b) an X-ray powder diffraction (XRPD) pattern with at least two of the characteristic peaks at 6.4±0.1° 2-Theta, 9.8±0.1° 2-Theta, 18.7±0.1° 2-Theta, 19.4±0.1° 2-Theta, 20.5±0.1° 2-Theta, 21.9±0.1° 2-Theta, 23.0±0.1° 2-Theta, and 25.4±0.1° 2-Theta;

(c) substantially the same X-ray powder diffraction (XRPD) pattern post-storage at 40° C. and 75% RH for at least a week (d) a DSC thermogram substantially the same as the one set forth in FIG. 36 ;

(e) a DSC thermogram with a sharp endotherm with an onset at about 100° C. and a peak at about 103° C., followed by two small endotherms; one with an onset at about 131° C. and a peak at about 137° C., and one with an onset at about 144° C. and a peak at about 150° C.;

or

(f) combinations thereof.

89 . The co-crystal of claim 88 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 35 .

90 . The co-crystal of claim 88 , wherein the co-crystal has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 6.4±0.1° 2-Theta, 9.8±0.1° 2-Theta, 18.7±0.1° 2-Theta, 19.4±0.1° 2-Theta, 20.5±0.1° 2-Theta, 21.9±0.1° 2-Theta, 23.0±0.1 2-Theta, and 25.4±0.1° 2-Theta.

91 . A pharmaceutical composition comprising a co-crystal of any one of claims 1 - 90 , and a pharmaceutically acceptable excipient.

92 . A method of treating cancer in a mammal in need thereof, comprising administering to the mammal a pharmaceutical composition according to claim 91 .

93 . The method of claim 92 , wherein the cancer is a B cell malignancy.

94 . The method of claim 92 , wherein the cancer is a B cell malignancy selected from chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), diffuse large B Cell lymphoma (DLBCL), and multiple myeloma.

95 . The method of claim 92 , wherein the cancer is a lymphoma, leukemia or a solid tumor.

96 . The method of claim 92 , wherein the cancer is diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic lymphoma, chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B cell lymphoma, nodal marginal zone B cell lymphoma, mantle cell lymphoma, mediastinal (thymic) large B cell lymphoma, intravascular large B cell lymphoma, primary effusion lymphoma, burkitt lymphoma/leukemia, or lymphomatoid granulomatosis.

97 . The method of any one of claims 92 - 96 , wherein the mammal is a human.