Polymorphs

Description

BACKGROUND OF THE INVENTION

This Application claims priority of EP 06 009 202, which is hereby incorporated by reference in its entirety.

1. Field of the Invention

The invention relates to polymorphous crystal modifications of a DPP-IV inhibitor, the preparation thereof and the use thereof for preparing a medicament.

2. Description of the Prior Art

The enzyme DPP-IV, also known by the name CD26, is a serine protease which promotes the cleaving of dipeptides in proteins with a proline or alanine group at the N-terminal end. DPP-IV inhibitors thereby influence the plasma level of bioactive peptides including the peptide GLP-1. Compounds of this type are useful for the prevention or treatment of illnesses or conditions which are associated with an increased DPP-IV activity or which can be prevented or alleviated by reducing the DPP-IV activity, particularly type I or type II diabetes mellitus, prediabetes, or reduced glucose tolerance.

WO 2004/018468 describes DPP-IV inhibitors with valuable pharmacological properties. One example of the inhibitors disclosed therein is 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the thermoanalysis of the anhydrous form A/B.

FIG. 2 shows a cyclic DSC diagram, in which the phase transition from −40° C. to 120° C. and vice versa has been run through a total of 3 times.

FIG. 3 shows an X-ray powder diagram of the anhydrous form A.

FIG. 4 shows an X-ray powder diagram of the anhydrous form B.

FIG. 5 shows an X-ray powder diagram of polymorph C.

FIG. 6 shows the thermoanalysis of form C.

DETAILED DESCRIPTION OF THE INVENTION

Within the scope of the present invention it has been found that 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine may take on various polymorphous crystal modifications and that the compound prepared in WO 2004/018468 is present at ambient temperature as a mixture of two enantiotropic polymorphs. The temperature at which the two polymorphs transform into one another is 25±15° C. (see FIGS. 1 and 2).

The pure high temperature form (polymorph A), which can be obtained by heating the mixture to temperatures >40° C., melts at 206±3° C. In the X-ray powder diagram (see FIG. 3) this form shows characteristic reflections at the following d values: 11.49 Å, 7.60 Å, 7.15 Å, 3.86 Å, 3.54 Å and 3.47 Å (cf. also Table 1 and 2).

Anhydrous polymorph A may be prepared by

(a) refluxing 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in absolute ethanol and optionally filtering the mixture,
(b) cooling the hot solution or the hot filtrate until crystallisation sets in,
(c) diluting with a solvent such as tert.-butylmethylether,
(d) suction filtering the solvent mixture and
(e) drying the polymorph A at 45° C. in vacuo.

The low temperature form (polymorph B) is obtained by cooling to temperatures <10° C. In the X-ray powder diagram (see FIG. 4) this form shows characteristic reflections at the following d values: 11.25 Å, 9.32 Å, 7.46 Å, 6.98 Å and 3.77 Å (cf. also Table 3 and 4).

Anhydrous polymorph B may be prepared by

(a) dissolving 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in absolute ethanol and refluxing and optionally filtering the mixture,
(b) cooling the hot solution or the hot filtrate for crystallisation to a temperature below 10° C.,
(c) diluting with a solvent such as tert.-butylmethylether,
(d) suction filtering the solvent mixture and
(e) drying the polymorph at a temperature below 10° C. in vacuo.

Another polymorph (polymorph C) shows characteristic reflections in the X-ray powder diagram (see FIG. 5) at the following d values: 12.90 Å, 11.10 Å, 6.44 Å, 3.93 Å and 3.74 Å (cf. also Table 5).

Polymorph C is obtained if

(a) 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine is dissolved in methanol and refluxed and optionally filtered in the presence of activated charcoal,
(b) the methanolic solution is cooled to a temperature of 40-60° C.,
(c) a solvent such as tert.-butylmethylether or diisopropylether is added,
(d) the resulting suspension is first of all cooled slowly to 15-25° C. and then later to 0-5° C.,
(e) the crystals formed are suction filtered and washed again with tert.-butylmethylether or diisopropylether and
(f) the crystals thus obtained are dried at a temperature of 70° C. in the vacuum dryer.

Another polymorph (polymorph D) melts at 150±3° C. This polymorph is obtained if polymorph C is heated to a temperature of 30-100° C. or dried at this temperature.

Finally, there is also polymorph E, which melts at a temperature of 175±3° C. Anhydrous polymorph E is formed if polymorph D is melted. On further heating, polymorph E crystallises out of the melt.

The polymorphs thus obtained may be used in the same way as the mixture of the two polymorphs A and B described in WO 2004/018468 for preparing a pharmaceutical composition which is suitable for treating patients with type I and type II diabetes mellitus, prediabetes or reduced glucose tolerance, with rheumatoid arthritis, obesity, or calcitonin-induced osteoporosis, as well as patients in whom an allograft transplant has been carried out. These medicaments contain in addition to one or more inert carriers at least 0.1% to 0.5%, preferably at least 0.5% to 1.5% and particularly preferably at least 1% to 3% of one of the polymorphs A, B, or C.

The following Examples are intended to illustrate the invention in more detail.

EXAMPLE 1
Crystallisation of Polymorph A

Crude 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine is refluxed with 5 times as much absolute ethanol and the hot solution is filtered clear through activated charcoal. After the filtrate has been cooled to 20° C. and crystallisation has set in, the solution is diluted to double the volume with tert.-butylmethylether. Then the suspension is cooled to 2° C., stirred for 2 hours, suction filtered and dried in the vacuum dryer at 45° C.

FIG. 1 shows the thermoanalysis of the anhydrous form A/B.

Polymorph A melts at 206±3° C. In the DSC diagram another slightly endothermic signal can be seen at approx. 25° C. This is a fully reversible solid-solid phase transition between the two enantiotropic crystal modifications A and B. The form A is the thermodynamically stable modification above this transformation temperature, w| form B is the thermodynamically stable modification below this transformation temperature.

FIG. 2 shows a cyclic DSC diagram, in which the phase transition from −40° C. to 120° C. and vice versa has been run through a total of 3 times. During heating, the phase transition is observed as an endothermic signal and, correspondingly, during cooling it is observed as an exothermic signal. During the first heating cycle the phase transition may also be observed as an endothermic double signal or as a very broad signal while in all the other cycles the signal occurs as a very sharp endothermic or exothermic signal, depending on whether heating or cooling is taking place.

FIG. 3 shows an X-ray powder diagram of the anhydrous form A

TABLE 1

Labelled X-ray reflections up to 30° 2 Θ with intensities

(standardised) for the anhydrous polymorph A

2 Θ
intensity
d_hkl
labelling
d_exp-calc

[°]
I/I_o[%]
[Å]
h
k
l
[Å]

5.56
1
15.89
1
0
0
−0.008

7.18
32
12.31
0
1
1
0.005

7.62
100
11.59
1
1
0
0.007

8.49
20
10.41
−1
1
1
0.002

9.91
24
8.92
0
0
2
0.003

10.41
18
8.49
0
2
0
0.024

11.18
24
7.91
2
0
0
0.038

11.63
41
7.60
−1
1
2
0.003

12.37
59
7.15
−1
2
1
−0.003

13.19
6
6.71
1
2
1
−0.014

13.45
3
6.58
−2
0
2
0.007

14.05
6
6.30
2
1
1
0.011

14.38
6
6.16
0
2
2
0.003

14.71
10
6.02
−1
2
2
−0.008

15.26
13
5.80
2
2
0
0.001

15.76
10
5.62
−1
1
3
0.008

16.09
1
5.51
1
2
2
−0.010

16.32
1
5.43
2
0
2
0.035

16.69
4
5.31
2
2
1
−0.007

17.03
3
5.20
−1
3
1
0.026

17.63
6
5.03
1
3
1
0.006

18.17
5
4.88
−1
2
3
−0.004

18.78
7
4.72
−1
3
2
−0.014

19.30
1
4.60
−2
3
1
−0.019

19.61
2
4.52
−3
2
1
0.036

19.86
20
4.47
−2
2
3
0.040

20.29
10
4.37
2
0
3
0.019

20.57
4
4.31
0
1
4
0.006

21.12
1
4.20
3
0
2
0.048

21.57
12
4.12
−2
1
4
0.028

22.46
10
3.96
1
4
1
0.035

23.03
35
3.86
4
1
0
0.022

23.39
21
3.80
−1
4
2
0.019

24.08
2
3.69
−3
1
4
−0.006

24.51
1
3.63
−4
0
3
0.036

24.91
10
3.57
−2
4
2
0.003

25.14
39
3.54
3
1
3
0.043

25.69
36
3.47
−3
3
3
0.041

26.68
3
3.34
0
5
1
0.035

26.90
2
3.31
3
4
0
0.027

27.10
2
3.29
0
2
5
0.030

27.42
3
3.25
4
3
0
0.006

28.19
2
3.16
−1
5
2
−0.035

28.54
2
3.12
3
0
4
0.047

28.94
11
3.08
0
4
4
−0.036

29.18
5
3.06
−4
3
3
0.017

29.50
4
3.03
−1
0
6
0.041

30.18
7
2.96
−1
5
3
−0.042

TABLE 2

Lattice metrics of the anhydrous form A

Symmetry:
monoclinic

space group:
P

a:
16.16(2)
Å

b:
17.02(1)
Å

c:
18.18(2)
Å

β:
100.95(6)°

cell volume:
4907(11)
Å³

EXAMPLE 2
Crystallisation of Polymorph B

Polymorph B is obtained by cooling form A from Example 1 to temperatures <10° C.

FIG. 4 shows an X-ray powder diagram of the anhydrous form B

TABLE 3

Labelled X-ray reflections up to 30° 2 Θ with intensities

(standardised) for the anhydrous form B

2 Θ
intensity
d_hkl
labelling
d_exp-calc

[°]
I/I_o[%]
[Å]
h
k
l
[Å]

5.82
3
15.17
1
0
0
−0.007

7.04
33
12.55
0
1
1
0.001

7.82
100
11.3
1
1
0
−0.004

8.84
11
10
−1
1
1
0.001

9.44
40
9.36
1
1
1
0.011

10.62
14
8.32
−1
0
2
0.013

10.79
24
8.19
0
1
2
−0.005

11.82
39
7.48
−1
1
2
−0.003

12.64
53
7
−1
2
1
−0.009

13.07
11
6.77
1
2
1
−0.006

13.24
6
6.68
−2
1
1
0.004

14.04
16
6.3
2
1
1
0.003

15.23
17
5.81
−2
1
2
0.003

15.70
22
5.64
2
2
0
0.016

16.38
2
5.41
0
3
1
−0.010

16.73
6
5.3
2
2
1
0.008

17.67
8
5.02
0
2
3
0.014

18.16
3
4.88
−1
2
3
0.005

18.33
9
4.84
3
1
0
0.016

18.48
10
4.8
−3
1
1
−0.003

18.97
15
4.68
0
0
4
−0.001

19.56
6
4.54
1
3
2
0.013

20.00
17
4.44
2
1
3
0.000

20.42
9
4.35
1
0
4
0.009

20.76
4
4.27
3
0
2
−0.014

20.97
4
4.23
0
4
0
0.010

21.07
5
4.21
1
1
4
−0.009

21.22
12
4.18
0
3
3
0.001

21.40
7
4.15
3
2
1
0.004

21.66
4
4.1
−1
3
3
0.018

21.98
7
4.04
2
2
3
−0.003

22.16
10
4.01
−3
1
3
0.008

22.97
3
3.87
1
2
4
−0.006

23.58
43
3.77
−2
3
3
−0.003

23.78
15
3.74
−2
2
4
−0.004

24.05
6
3.7
4
1
0
−0.002

24.29
8
3.66
−2
4
1
−0.008

24.46
5
3.64
3
3
1
0.018

24.71
7
3.6
0
3
4
0.001

24.96
23
3.56
2
3
3
−0.001

25.45
12
3.5
−2
4
2
−0.010

25.75
35
3.46
4
2
0
0.011

25.99
4
3.43
3
2
3
0.014

26.15
6
3.41
3
3
2
0.010

26.57
12
3.35
−2
3
4
−0.001

26.82
4
3.32
−3
2
4
0.011

27.20
6
3.28
1
2
5
−0.010

27.43
4
3.25
−2
4
3
−0.003

27.60
3
3.23
−2
2
5
−0.005

28.19
4
3.16
3
4
1
0.010

28.40
15
3.14
0
4
4
−0.013

28.64
12
3.11
0
0
6
0.016

29.18
6
3.06
−4
3
2
0.004

29.42
2
3.03
1
4
4
0.002

29.99
10
2.98
0
5
3
−0.008

30.77
3
2.9
−4
3
3
0.018

TABLE 4

Lattice metrics of the anhydrous form B

Symmetry:
monoclinic

space group:
P2₁/c (# 14)

a:
15.23(1)
Å

b:
16.94(1)
Å

c:
18.79(1)
Å

β:
95.6(2)°

cell volume:
4823(3)
Å³

EXAMPLE 3
Crystallisation of Polymorph C

Crude 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine (26 kg) is refluxed with 157 I methanol, combined with 1.3 kg of activated charcoal and after 30 minutes' stirring the mixture is filtered and rinsed with 26 I methanol. 122 I of methanol are distilled off from the filtrate, then the residue is cooled to 45-55° C. 52 I of tert.-butylmethylether are added to the residue over 30 minutes. Then the mixture is stirred for another 60 minutes at 45-55° C. Crystallisation takes place within this time. A further 78 I tert. butylmethylether are added to the suspension over 30 minutes and then it is stirred again for a further 60 minutes at 45-55° C. It is diluted to four times the volume. The suspension is slowly cooled to 15-25° C. and stirred overnight at this temperature. After the suspension has been cooled to 0-5° C. the crystals are suction filtered, washed with 2 batches tert.-butylmethylether and dried at 70° C. in the vacuum dryer.

FIG. 5 shows an X-ray powder diagram of polymorph C

TABLE 5

X-ray reflections up to 30° 2 Θ with intensities

(standardised) for the anhydrous form C

2 Θ
d_hkl
intensity

[°]
[Å]
I/I_o[%]

3.38
26.16
4

6.85
12.90
100

7.18
12.31
11

7.52
11.74
14

7.96
11.10
36

9.80
9.02
3

11.11
7.96
2

11.58
7.64
3

12.30
7.19
5

13.30
6.65
16

13.75
6.44
26

14.38
6.16
17

14.74
6.01
11

14.95
5.92
10

15.63
5.66
6

16.28
5.44
5

17.81
4.98
10

18.33
4.83
6

18.75
4.73
15

20.51
4.33
8

20.77
4.27
8

21.47
4.14
3

21.96
4.05
4

22.59
3.93
26

23.76
3.74
29

24.68
3.60
6

25.01
3.56
7

25.57
3.48
4

25.96
3.43
4

26.93
3.31
18

27.22
3.27
13

27.92
3.19
10

EXAMPLE 4
Crystallisation of Polymorph D

Polymorph D is obtained if polymorph C from Example 3 is heated to a temperature of 30-100° C. or dried at this temperature.

EXAMPLE 5
Crystallisation of Polymorph E

Anhydrous polymorph E is obtained if polymorph D is melted. On further heating, polymorph E crystallises out of the melt.

FIG. 6 shows a thermoanalysis of form C

In the DSC diagram of form C a whole range of signals can be observed. The strongest signal is the melting point of the anhydrous form A at approx. 206° C., which is produced in the DSC experiment. Before the melting point a number of other endothermic and exothermic signals can be observed. Thus, for example, a very broad and weak endothermic signal can be seen between 30 and 100° C., which correlates with the main loss of weight in thermogravimetry (TR). A TG/IR coupling experiment provides the information that only water escapes from the sample in this temperature range.

An X-ray powder diagram taken of a sample maintained at a temperature of 100° C. shows different X-ray reflections from the starting material, suggesting that form C is a hydrate phase with stoichiometry somewhere in the region of a hemihydrate or monohydrate. The temperature-controlled sample is another anhydrous modification D, which only stable under anhydrous conditions. The D form melts at approx. 150° C. Another anhydrous crystal modification E crystallises from the melt, and when heated further melts at approx. 175° C. Finally, form A crystallises from the melt of form E. Form E is also a metastable crystal modification which occurs only at high temperatures.

Claims

1. An anhydrous polymorph A of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, characterised in that it melts at 206±3° C.
2. The polymorph A according to claim 1, characterised in that in the X-ray powder diagram it has characteristic reflections at the following d values: 11.59 A, 7.60 Å, 7.15 Å, 3.86 Å, 3.54 Å and 3.47 Å.
3. An anhydrous polymorph B of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, characterised in that at a temperature of 10-40° C. it transforms reversibly into the polymorph A of claim 1.
4. The polymorph according to claim 3, characterised in that in the X-ray powder diagram it has alia characteristic reflections at the following d values: 11.3 Å, 9.36 Å, 7.48 Å, 7 Å and 3.77 Å.
5. An anhydrous polymorph E of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, characterised in that it melts at 175±3° C.
6. A pharmaceutical composition comprising polymorph A according to claim 1, and one or more inert carriers or diluents.
7. A medicament containing 0.1% to 0.5% or 0.5% to 1.5% or 1% to 3% of polymorph A according to claim 1, in addition to one or more inert carriers.
8. A pharmaceutical composition comprising polymorph B according to claim 3, and one or more inert carriers or diluents.
9. A medicament containing 0.1% to 0.5% or 0.5% to 1.5% or 1% to 3% of polymorph B according to claim 3, in addition to one or more inert carriers.
10. The anhydrous polymorph A according to claim 1, characterized by its lattice metrics:
11. The anhydrous polymorph A according to claim 2, wherein the reflection at 11.59 A in the X-ray powder diagram has a relative intensity of 100%.
12. The anhydrous polymorph A according to claim 11, wherein the X-ray powder diagram exhibits no reflections having a relative intensity of 1% or more at the following d values: 11.3 Å, 9.36 Å, 7.48 Å, and 7 Å.
13. The anhydrous polymorph B according to claim 3, characterised by its lattice metrics:
14. The anhydrous polymorph B according to claim 4, wherein the reflection at 11.3 Å in the X-ray powder diagram has a relative intensity of 100%.
15. The anhydrous polymorph B according to claim 14, wherein the X-ray powder diagram exhibits no reflections having a relative intensity of 1% or more at the following d values: 11.59 Å, 7.60 Å, and 7.15 Å.
16. A pharmaceutical composition comprising polymorph A, as defined in claim 1 and one or more inert carriers.
17. A pharmaceutical composition comprising polymorph B, as defined in claim 3 and one or more inert carriers.
18. The medicament according to claim 7, containing 0.1% to 0.5% of the polymorph A.
19. The medicament according to claim 7, containing 0.5% to 1.5% of the polymorph A.
20. The medicament according to claim 7, containing 1% to 3% of the polymorph A.
21. The medicament according to claim 9, containing 0.1% to 0.5% of the polymorph B.
22. The medicament according to claim 9, containing 0.5% to 1.5% of the polymorph B.
23. The medicament according to claim 9, containing 1% to 3% of the polymorph B.
24. A pharmaceutical composition comprising polymorph A, as defined in claim 2 and one or more inert carriers.
25. A pharmaceutical composition comprising polymorph B, as defined in claim 4 and one or more inert carriers.
26. A medicament containing 0.1% to 0.5% or 0.5% to 1.5% or 1% to 3% of polymorph A as defined in claim 2, in addition to one or more inert carriers.
27. A medicament containing 0.1% to 0.5% or 0.5% to 1.5% or 1% to 3% of polymorph B as defined in claim in addition to one or more inert carriers.
28. The medicament according to claim 26, containing 0.1% to 0.5% of the polymorph A.
29. The medicament according to claim 26, containing 0.5% to 1.5% of the polymorph A.
30. The medicament according to claim 26, containing 1% to 3% of the polymorph A.
31. The medicament according to claim 27, containing 0.1% to 0.5% of the polymorph B.
32. The medicament according to claim 27, containing 0.5% to 1.5% of the polymorph B.
33. The medicament according to claim 27, containing 1% to 3% of the polymorph B.
34. The medicament according to claim 26, wherein the polymorph A has reflection at 11.59 A in the X-ray powder diagram having a relative intensity of 100%, and wherein the X-ray powder diagram exhibits no reflections having a relative intensity of 1% or more at the following d values: 11.3 Å, 9.36 Å, 7.48 Å, and 7 Å.
35. The medicament according to claim 27, wherein the polymorph B has reflection at 11.3 Å in the X-ray powder diagram having a relative intensity of 100%, and wherein the X-ray powder diagram exhibits no reflections having a relative intensity of 1% or more at the following d values: 11.59 Å, 7.60 Å, and 7.15 Å.

Priority Claims (1)

Number	Date	Country	Kind
06009202	May 2006	EP	regional

US Referenced Citations (379)

Number	Name	Date	Kind
2056046	Fourneau	Sep 1936	A
2375138	Victors	May 1945	A
2629736	Krimmel	Feb 1953	A
2730544	Sahyun	Jan 1956	A
2750387	Krimmel	Jun 1956	A
2928833	Leake et al.	Mar 1960	A
3174901	Sterne	Mar 1965	A
3236891	Seemuller	Feb 1966	A
3454635	Muth	Jul 1969	A
3673241	Marxer	Jun 1972	A
3925357	Okada et al.	Dec 1975	A
4005208	Bender et al.	Jan 1977	A
4061753	Bodor et al.	Dec 1977	A
4159345	Takeo et al.	Jun 1979	A
4382091	Benjamin et al.	May 1983	A
4599338	Regnier et al.	Jul 1986	A
4639436	Junge et al.	Jan 1987	A
4687777	Meguro et al.	Aug 1987	A
4743450	Harris et al.	May 1988	A
4764466	Suyama et al.	Aug 1988	A
4816455	Schickaneder et al.	Mar 1989	A
4873330	Lindholm	Oct 1989	A
4968672	Jacobson et al.	Nov 1990	A
5034225	Bennett et al.	Jul 1991	A
5041448	Janssens et al.	Aug 1991	A
5051509	Nagano et al.	Sep 1991	A
5051517	Findeisen et al.	Sep 1991	A
5084460	Munson, Jr. et al.	Jan 1992	A
5120712	Habener	Jun 1992	A
5130244	Nishimaki et al.	Jul 1992	A
5164526	Macher	Nov 1992	A
5219870	Kim	Jun 1993	A
5223499	Greenlee et al.	Jun 1993	A
5234897	Findeisen et al.	Aug 1993	A
5258380	Janssens et al.	Nov 1993	A
5266555	Findeisen et al.	Nov 1993	A
5273995	Roth	Dec 1993	A
5284967	Macher	Feb 1994	A
5300298	LaNoue	Apr 1994	A
5329025	Wong et al.	Jul 1994	A
5332744	Chakravarty et al.	Jul 1994	A
5389642	Dorsch et al.	Feb 1995	A
5399578	Buhlmayer et al.	Mar 1995	A
5407929	Takahashi et al.	Apr 1995	A
5461066	Gericke et al.	Oct 1995	A
5470579	Bonte et al.	Nov 1995	A
5591762	Hauel et al.	Jan 1997	A
5594003	Hauel et al.	Jan 1997	A
5602127	Hauel et al.	Feb 1997	A
5614519	Hauel et al.	Mar 1997	A
5719279	Kufner-Muhl et al.	Feb 1998	A
5728849	Bouchard et al.	Mar 1998	A
5753635	Buckman et al.	May 1998	A
5830908	Grunenberg et al.	Nov 1998	A
5879708	Makino et al.	Mar 1999	A
5958951	Ahrndt et al.	Sep 1999	A
5965555	Gebert et al.	Oct 1999	A
5965592	Buhlmayer et al.	Oct 1999	A
6011049	Whitcomb	Jan 2000	A
6107302	Carter et al.	Aug 2000	A
6166063	Villhauer	Dec 2000	A
6200958	Odaka et al.	Mar 2001	B1
6248758	Klokkers et al.	Jun 2001	B1
6303661	Demuth et al.	Oct 2001	B1
6342601	Bantick et al.	Jan 2002	B1
6372940	Cavazza	Apr 2002	B1
6399101	Frontanes et al.	Jun 2002	B1
6448323	Jordan et al.	Sep 2002	B1
6548481	Demuth et al.	Apr 2003	B1
6579868	Asano et al.	Jun 2003	B1
6689353	Wang et al.	Feb 2004	B1
6699845	Asahi	Mar 2004	B2
6727261	Gobbi et al.	Apr 2004	B2
6784195	Hale et al.	Aug 2004	B2
6821978	Chackalamannil et al.	Nov 2004	B2
6869947	Kanstrup et al.	Mar 2005	B2
6890898	Bachovchin et al.	May 2005	B2
6995183	Hamann et al.	Feb 2006	B2
7034039	Oi et al.	Apr 2006	B2
7060722	Kitajima et al.	Jun 2006	B2
7074794	Kitajima et al.	Jul 2006	B2
7074798	Yoshikawa et al.	Jul 2006	B2
7074923	Dahanukar et al.	Jul 2006	B2
7109192	Hauel et al.	Sep 2006	B2
7179809	Eckhardt et al.	Feb 2007	B2
7183280	Himmelsbach et al.	Feb 2007	B2
7192952	Kanstrup et al.	Mar 2007	B2
7217711	Eckhardt et al.	May 2007	B2
7220750	Himmelsbach et al.	May 2007	B2
7235538	Kanstrup et al.	Jun 2007	B2
7247478	Eberhardt et al.	Jul 2007	B2
7282219	Nomura et al.	Oct 2007	B2
7291642	Kauffmann-Hefner et al.	Nov 2007	B2
7361687	Barth et al.	Apr 2008	B2
7393847	Eckhardt et al.	Jul 2008	B2
7407955	Himmelsbach et al.	Aug 2008	B2
7432262	Eckhardt et al.	Oct 2008	B2
7439370	Eckhardt	Oct 2008	B2
7470716	Eckhardt et al.	Dec 2008	B2
7476671	Eckhardt et al.	Jan 2009	B2
7482337	Himmelsbach et al.	Jan 2009	B2
7495002	Langkopf et al.	Feb 2009	B2
7495003	Eckhardt et al.	Feb 2009	B2
7495005	Himmelsbach et al.	Feb 2009	B2
7501426	Himmelsbach et al.	Mar 2009	B2
7550455	Himmelsbach et al.	Jun 2009	B2
7560450	Eckhardt et al.	Jul 2009	B2
7566707	Eckhardt et al.	Jul 2009	B2
7569574	Maier et al.	Aug 2009	B2
7579449	Eckhardt et al.	Aug 2009	B2
7610153	Carter, Jr. et al.	Oct 2009	B2
7645763	Himmelsbach et al.	Jan 2010	B2
7718666	Boehringer et al.	May 2010	B2
7754481	Eberhardt et al.	Jul 2010	B2
7799782	Munson et al.	Sep 2010	B2
7820815	Pfrengle et al.	Oct 2010	B2
7838529	Himmelsbach et al.	Nov 2010	B2
7919572	Angot et al.	Apr 2011	B2
8039477	Hendrix et al.	Oct 2011	B2
8071583	Himmelsbach	Dec 2011	B2
8106060	Pfrengle et al.	Jan 2012	B2
8119648	Himmelsbach et al.	Feb 2012	B2
8158633	Hendrix et al.	Apr 2012	B2
8178541	Himmelsbach et al.	May 2012	B2
8232281	Dugi et al.	Jul 2012	B2
8338450	Arora et al.	Dec 2012	B2
8399414	Harada et al.	Mar 2013	B2
8455435	Franz et al.	Jun 2013	B2
8513264	Mark et al.	Aug 2013	B2
8541450	Pfrengle et al.	Sep 2013	B2
8637530	Pfrengle et al.	Jan 2014	B2
8664232	Himmelsbach et al.	Mar 2014	B2
8673927	Dugi et al.	Mar 2014	B2
8679520	Horres et al.	Mar 2014	B2
8697868	Himmelsbach et al.	Apr 2014	B2
8785455	Hotter et al.	Jul 2014	B2
8846695	Dugi	Sep 2014	B2
8853156	Dugi et al.	Oct 2014	B2
8865729	Sieger et al.	Oct 2014	B2
8883800	Pfrengle et al.	Nov 2014	B2
8883805	Pfrengle et al.	Nov 2014	B2
8962636	Pfrengle et al.	Feb 2015	B2
9034883	Klein et al.	May 2015	B2
9108964	Himmelsbach et al.	Aug 2015	B2
9149478	Klein et al.	Oct 2015	B2
9155705	Friedl et al.	Oct 2015	B2
9173859	Dugi et al.	Nov 2015	B2
9186392	Klein et al.	Nov 2015	B2
9199998	Pfrengle et al.	Dec 2015	B2
9212183	Sieger et al.	Dec 2015	B2
9266888	Sieger	Feb 2016	B2
9321791	Himmelsbach et al.	Apr 2016	B2
9415016	Friedl et al.	Aug 2016	B2
9486426	Eller	Aug 2016	B2
9457029	Dugi et al.	Oct 2016	B2
9486526	Dugi	Nov 2016	B2
9493462	Sieger	Nov 2016	B2
9815837	Sieger	Nov 2017	B2
10023574	Himmelsbach	Jul 2018	B2
10034877	Dugi	Jul 2018	B2
10155000	Meinicke et al.	Dec 2018	B2
10301313	Sieger	May 2019	B2
20010020006	Demuth et al.	Sep 2001	A1
20010051646	Demuth et al.	Dec 2001	A1
20020019411	Robl et al.	Feb 2002	A1
20020042393	Oobae et al.	Apr 2002	A1
20020115718	Chen et al.	Aug 2002	A1
20020137903	Ellsworth et al.	Sep 2002	A1
20020160047	Hussain et al.	Oct 2002	A1
20020161001	Kanstrup et al.	Oct 2002	A1
20020169174	Chackalamannil et al.	Nov 2002	A1
20020198205	Himmelsbach et al.	Dec 2002	A1
20030040490	Sugiyama et al.	Feb 2003	A1
20030078269	Pearson et al.	Apr 2003	A1
20030100563	Edmondson et al.	May 2003	A1
20030104053	Gusler et al.	Jun 2003	A1
20030104983	DeFelippis et al.	Jun 2003	A1
20030105077	Kanstrup et al.	Jun 2003	A1
20030114390	Washburn et al.	Jun 2003	A1
20030130313	Fujino et al.	Jul 2003	A1
20030149071	Gobbi et al.	Aug 2003	A1
20030153509	Bachovchin et al.	Aug 2003	A1
20030166578	Arch et al.	Sep 2003	A1
20030199528	Kanstrup et al.	Oct 2003	A1
20030224043	Appel et al.	Dec 2003	A1
20030232987	Dahanukar et al.	Dec 2003	A1
20030236272	Carr	Dec 2003	A1
20040018468	Gorokhovsky	Jan 2004	A1
20040023981	Ren et al.	Feb 2004	A1
20040034014	Kanstrup et al.	Feb 2004	A1
20040037883	Zhou et al.	Feb 2004	A1
20040063725	Barth et al.	Apr 2004	A1
20040077645	Himmelsbach et al.	Apr 2004	A1
20040082570	Yoshikawa et al.	Apr 2004	A1
20040087587	Himmelsbach et al.	May 2004	A1
20040097510	Himmelsbach et al.	May 2004	A1
20040116328	Yoshikawa et al.	Jun 2004	A1
20040122048	Benjamin et al.	Jun 2004	A1
20040122228	Maier et al.	Jun 2004	A1
20040126358	Warne et al.	Jul 2004	A1
20040138214	Himmelsbach et al.	Jul 2004	A1
20040138215	Eckhardt et al.	Jul 2004	A1
20040152659	Matsuoka et al.	Aug 2004	A1
20040152720	Hartig et al.	Aug 2004	A1
20040166125	Himmelsbach et al.	Aug 2004	A1
20040171836	Fujino et al.	Sep 2004	A1
20040180925	Matsuno et al.	Sep 2004	A1
20040259903	Boehringer et al.	Dec 2004	A1
20040266806	Sanghvi et al.	Dec 2004	A1
20050020484	Harada et al.	Jan 2005	A1
20050020574	Hauel et al.	Jan 2005	A1
20050026921	Eckhardt et al.	Feb 2005	A1
20050027012	Kohlrausch	Feb 2005	A1
20050031682	Cucala Escoi et al.	Feb 2005	A1
20050032804	Cypes et al.	Feb 2005	A1
20050065145	Cao et al.	Mar 2005	A1
20050070562	Jones et al.	Mar 2005	A1
20050070594	Kauschke et al.	Mar 2005	A1
20050070694	Gelfanova et al.	Mar 2005	A1
20050097798	Evans et al.	May 2005	A1
20050107730	Doty et al.	May 2005	A1
20050119162	Harada et al.	Jun 2005	A1
20050130985	Himmelsbach et al.	Jun 2005	A1
20050143377	Himmelsbach et al.	Jun 2005	A1
20050171093	Eckhardt et al.	Aug 2005	A1
20050187227	Himmelsbach et al.	Aug 2005	A1
20050203095	Eckhardt et al.	Sep 2005	A1
20050234108	Himmelsbach et al.	Oct 2005	A1
20050234235	Eckhardt et al.	Oct 2005	A1
20050239778	Konetzki et al.	Oct 2005	A1
20050244502	Mathias et al.	Nov 2005	A1
20050256310	Hulin et al.	Nov 2005	A1
20050261271	Feng et al.	Nov 2005	A1
20050261352	Eckhardt	Nov 2005	A1
20050266080	Desai et al.	Dec 2005	A1
20050276794	Papas et al.	Dec 2005	A1
20060004074	Eckhardt et al.	Jan 2006	A1
20060008829	Hess	Jan 2006	A1
20060034922	Cheng et al.	Feb 2006	A1
20060039968	Manikandan et al.	Feb 2006	A1
20060039974	Akiyama et al.	Feb 2006	A1
20060047125	Leonardi et al.	Mar 2006	A1
20060058323	Eckhardt et al.	Mar 2006	A1
20060063787	Yoshikawa et al.	Mar 2006	A1
20060074058	Holmes et al.	Apr 2006	A1
20060079541	Langkopf et al.	Apr 2006	A1
20060094722	Yasuda et al.	May 2006	A1
20060100199	Yoshikawa et al.	May 2006	A1
20060106035	Hendrix et al.	May 2006	A1
20060111372	Hendrix et al.	May 2006	A1
20060111379	Guillemont et al.	May 2006	A1
20060134206	Iyer et al.	Jun 2006	A1
20060142310	Pfrengle et al.	Jun 2006	A1
20060154866	Chu et al.	Jul 2006	A1
20060159746	Troup et al.	Jul 2006	A1
20060173056	Kitajima et al.	Aug 2006	A1
20060205711	Himmelsbach et al.	Sep 2006	A1
20060205943	Dahanukar et al.	Sep 2006	A1
20060247226	Himmelsbach et al.	Nov 2006	A1
20060270668	Chew et al.	Nov 2006	A1
20060270701	Kroth et al.	Nov 2006	A1
20070027168	Pfrengle et al.	Feb 2007	A1
20070059797	Low et al.	Mar 2007	A1
20070060530	Christopher et al.	Mar 2007	A1
20070072803	Chu et al.	Mar 2007	A1
20070072810	Asakawa	Mar 2007	A1
20070088038	Eckhardt et al.	Apr 2007	A1
20070093659	Bonfanti et al.	Apr 2007	A1
20070142383	Eckhardt et al.	Jun 2007	A1
20070173452	DiMarchi et al.	Jul 2007	A1
20070185091	Himmelsbach et al.	Aug 2007	A1
20070196472	Kiel et al.	Aug 2007	A1
20070197522	Edwards et al.	Aug 2007	A1
20070197552	Carr	Aug 2007	A1
20070219178	Muramoto	Sep 2007	A1
20070254944	Hughes	Nov 2007	A1
20070259880	Sakashita et al.	Nov 2007	A1
20070259900	Sieger et al.	Nov 2007	A1
20070259925	Boehringer et al.	Nov 2007	A1
20070259927	Suzuki et al.	Nov 2007	A1
20070265349	Rapin et al.	Nov 2007	A1
20070281940	Dugi et al.	Dec 2007	A1
20070299076	Piotrowski et al.	Dec 2007	A1
20080014270	Harada	Jan 2008	A1
20080039427	Ray et al.	Feb 2008	A1
20080107731	Kohlrausch et al.	May 2008	A1
20080108816	Zutter	May 2008	A1
20080221200	Allison et al.	Sep 2008	A1
20080234291	Francois et al.	Sep 2008	A1
20080249089	Himmelsbach et al.	Oct 2008	A1
20080255159	Himmelsbach et al.	Oct 2008	A1
20080312243	Eckhardt et al.	Dec 2008	A1
20080318922	Nakahira et al.	Dec 2008	A1
20090023920	Eckhardt	Jan 2009	A1
20090054303	Gougoutas et al.	Feb 2009	A1
20090082256	Abe et al.	Mar 2009	A1
20090088408	Meade et al.	Apr 2009	A1
20090088569	Eckhardt et al.	Apr 2009	A1
20090093457	Himmelsbach et al.	Apr 2009	A1
20090131432	Himmelsbach et al.	May 2009	A1
20090136596	Munson et al.	May 2009	A1
20090137801	Himmelsbach et al.	May 2009	A1
20090149483	Nakahira et al.	Jun 2009	A1
20090186086	Shankar et al.	Jul 2009	A1
20090192314	Pfrengle et al.	Jul 2009	A1
20090253752	Burkey et al.	Oct 2009	A1
20090297470	Franz	Dec 2009	A1
20090301105	Loerting	Dec 2009	A1
20090325926	Himmelsbach	Dec 2009	A1
20100074950	Sesha	Mar 2010	A1
20100092551	Nakamura et al.	Apr 2010	A1
20100173916	Himmelsbach et al.	Jul 2010	A1
20100179191	Himmelsbach et al.	Jul 2010	A1
20100183531	Johncock et al.	Jul 2010	A1
20100204250	Himmelsbach et al.	Aug 2010	A1
20100209506	Eisenreich	Aug 2010	A1
20100310664	Watson et al.	Dec 2010	A1
20100317575	Pinnetti et al.	Dec 2010	A1
20100330177	Pourkavoos	Dec 2010	A1
20110009391	Braun et al.	Jan 2011	A1
20110028391	Holst et al.	Feb 2011	A1
20110046076	Eickelmann et al.	Feb 2011	A1
20110065731	Dugi et al.	Mar 2011	A1
20110092510	Klein et al.	Apr 2011	A1
20110098240	Dugi et al.	Apr 2011	A1
20110112069	Himmelsbach et al.	May 2011	A1
20110144083	Himmelsbach et al.	Jun 2011	A1
20110144095	Himmelsbach et al.	Jun 2011	A1
20110190322	Klein et al.	Aug 2011	A1
20110195917	Dugi et al.	Aug 2011	A1
20110206766	Friedl et al.	Aug 2011	A1
20110212982	Christopher et al.	Sep 2011	A1
20110263493	Dugi et al.	Oct 2011	A1
20110263617	Mark et al.	Oct 2011	A1
20110275561	Graefe-Mody et al.	Nov 2011	A1
20110301182	Dugi	Dec 2011	A1
20120003313	Kohlrausch et al.	Jan 2012	A1
20120035158	Himmelsbach et al.	Feb 2012	A1
20120040982	Himmelsbach et al.	Feb 2012	A1
20120053173	Banno et al.	Mar 2012	A1
20120094894	Graefe-Mody et al.	Apr 2012	A1
20120107398	Schneider et al.	May 2012	A1
20120121530	Klein et al.	May 2012	A1
20120122776	Graefe-Mody et al.	May 2012	A1
20120129874	Sieger et al.	May 2012	A1
20120142712	Pfrengle et al.	Jun 2012	A1
20120165251	Klein et al.	Jun 2012	A1
20120208831	Himmelsbach et al.	Aug 2012	A1
20120219622	Kohlrausch et al.	Aug 2012	A1
20120219623	Meinicke	Aug 2012	A1
20120232004	Bachovchin et al.	Sep 2012	A1
20120252782	Himmelsbach et al.	Oct 2012	A1
20120252783	Himmelsbach et al.	Oct 2012	A1
20120296091	Sieger et al.	Nov 2012	A1
20130064887	Ito et al.	Mar 2013	A1
20130122089	Kohlrausch et al.	May 2013	A1
20130172244	Klein et al.	Jul 2013	A1
20130184204	Pfrengle et al.	Jul 2013	A1
20130196898	Dugi et al.	Aug 2013	A1
20130236543	Ito et al.	Sep 2013	A1
20130303554	Klein et al.	Nov 2013	A1
20130310398	Mark et al.	Nov 2013	A1
20130315975	Klein et al.	Nov 2013	A1
20130317046	Johansen	Nov 2013	A1
20130324463	Klein et al.	Dec 2013	A1
20140100236	Busl et al.	Apr 2014	A1
20140274889	Johansen et al.	Sep 2014	A1
20140315832	Broedl et al.	Oct 2014	A1
20140343014	Klein et al.	Nov 2014	A1
20140371243	Klein et al.	Dec 2014	A1
20150196565	Klein et al.	Jul 2015	A1
20150246045	Klein et al.	Sep 2015	A1
20150265538	Balthes et al.	Sep 2015	A1
20160058769	Graefe-Mody et al.	Mar 2016	A1
20160082011	Klein et al.	Mar 2016	A1
20160106677	Boeck et al.	Apr 2016	A1
20160310435	Friedl et al.	Oct 2016	A1
20170020868	Dugi et al.	Jan 2017	A1
20170354660	Meinicke et al.	Dec 2017	A1

Foreign Referenced Citations (388)

Number	Date	Country
2003280680	Jun 2004	AU
2009224546	Sep 2009	AU
1123437	May 1982	CA
2136288	May 1995	CA
2375779	May 2000	CA
2418656	Feb 2002	CA
2435730	Sep 2002	CA
2496249	Mar 2004	CA
2496325	Mar 2004	CA
2498423	Apr 2004	CA
2505389	May 2004	CA
2508233	Jun 2004	CA
2529729	Dec 2004	CA
2543074	Jun 2005	CA
2555050	Sep 2005	CA
2556064	Sep 2005	CA
2558067	Oct 2005	CA
2558446	Oct 2005	CA
2561210	Oct 2005	CA
2562859	Nov 2005	CA
2576294	Mar 2006	CA
2590912	Jun 2006	CA
2599419	Nov 2006	CA
2651019	Nov 2007	CA
2651089	Nov 2007	CA
2720450	Oct 2009	CA
101035522	Sep 2007	CN
101234105	Aug 2008	CN
101309689	Nov 2008	CN
101590007	Dec 2009	CN
104130258	Nov 2014	CN
2205815	Aug 1973	DE
2758025	Jul 1979	DE
19705233	Aug 1998	DE
10109021	Sep 2002	DE
10117803	Oct 2002	DE
10238243	Mar 2004	DE
102004019540	Nov 2005	DE
102004024454	Dec 2005	DE
102004044221	Mar 2006	DE
102004054054	May 2006	DE
201300121	Oct 2009	EA
0023032	Jan 1981	EP
0149578	Jul 1985	EP
0189941	Aug 1986	EP
0223403	May 1987	EP
0237608	Sep 1987	EP
0248634	Dec 1987	EP
0342675	Nov 1989	EP
0389282	Sep 1990	EP
0399285	Nov 1990	EP
0400974	Dec 1990	EP
409281	Jan 1991	EP
0412358	Feb 1991	EP
443983	Aug 1991	EP
0475482	Mar 1992	EP
0524482	Jan 1993	EP
0638567	Feb 1995	EP
0657454	Jun 1995	EP
0775704	May 1997	EP
0950658	Oct 1999	EP
1054012	Nov 2000	EP
1066265	Jan 2001	EP
1310245	May 2003	EP
1333033	Aug 2003	EP
1338595	Aug 2003	EP
1406873	Apr 2004	EP
1500403	Jan 2005	EP
1514552	Mar 2005	EP
1523994	Apr 2005	EP
1535906	Jun 2005	EP
1537880	Jun 2005	EP
1557165	Jul 2005	EP
1586571	Oct 2005	EP
1743655	Jan 2007	EP
1760076	Mar 2007	EP
1829877	Sep 2007	EP
1852108	Nov 2007	EP
1897892	Mar 2008	EP
2143443	Jan 2010	EP
2166007	Mar 2010	EP
2308878	Apr 2011	EP
385302	Apr 1973	ES
2256797	Jul 2006	ES
2263057	Dec 2006	ES
2707641	Jan 1995	FR
2084580	Apr 1982	GB
9003243	May 1990	HU
9902308	Jul 2000	HU
S374895	Jun 1962	JP
61030567	Feb 1986	JP
770120	Mar 1995	JP
8333339	Dec 1996	JP
11193270	Jul 1999	JP
2000502684	Mar 2000	JP
2001213770	Aug 2001	JP
2001278812	Oct 2001	JP
2001292388	Oct 2001	JP
2002348279	Dec 2002	JP
2003286287	Oct 2003	JP
2003300977	Oct 2003	JP
2004161749	Jun 2004	JP
2004196824	Jul 2004	JP
2004250336	Sep 2004	JP
2005511636	Apr 2005	JP
2005519059	Jun 2005	JP
2006503013	Jan 2006	JP
2006045156	Feb 2006	JP
2006137678	Jun 2006	JP
2007501231	Jan 2007	JP
2007510059	Apr 2007	JP
2007522251	Aug 2007	JP
2007531780	Nov 2007	JP
2008513390	May 2008	JP
2008536881	Sep 2008	JP
2010500326	Jan 2010	JP
2010053576	Mar 2010	JP
2010070576	Apr 2010	JP
2010524580	Jul 2010	JP
2010535850	Nov 2010	JP
2010536734	Dec 2010	JP
2011088838	May 2011	JP
2011529945	Dec 2011	JP
2012502081	Jan 2012	JP
2012505859	Mar 2012	JP
20070111099	Nov 2007	KR
8706941	Nov 1987	WO
199107945	Jun 1991	WO
199205175	Apr 1992	WO
199219227	Nov 1992	WO
199402150	Feb 1994	WO
199403456	Feb 1994	WO
1994012200	Jun 1994	WO
9532178	Nov 1995	WO
199609045	Mar 1996	WO
199611917	Apr 1996	WO
199636638	Nov 1996	WO
199718814	May 1997	WO
199723447	Jul 1997	WO
199723473	Jul 1997	WO
199728808	Aug 1997	WO
199746526	Dec 1997	WO
1998007725	Feb 1998	WO
199811893	Mar 1998	WO
9818770	May 1998	WO
199822464	May 1998	WO
199828007	Jul 1998	WO
199840069	Sep 1998	WO
1998046082	Oct 1998	WO
199856406	Dec 1998	WO
199929695	Jun 1999	WO
1999038501	Aug 1999	WO
199950248	Oct 1999	WO
1999049857	Oct 1999	WO
199956561	Nov 1999	WO
199967279	Dec 1999	WO
2000003735	Jan 2000	WO
200012064	Mar 2000	WO
200072873	May 2000	WO
200034241	Jun 2000	WO
0069464	Nov 2000	WO
0072799	Dec 2000	WO
0078735	Dec 2000	WO
200072973	Dec 2000	WO
200073307	Dec 2000	WO
200107441	Feb 2001	WO
2001032158	May 2001	WO
2001040180	Jun 2001	WO
200152825	Jul 2001	WO
200152852	Jul 2001	WO
2001047514	Jul 2001	WO
2001051919	Jul 2001	WO
2001066548	Sep 2001	WO
2001068603	Sep 2001	WO
2001068646	Sep 2001	WO
200177110	Oct 2001	WO
2001072290	Oct 2001	WO
200196301	Dec 2001	WO
200197808	Dec 2001	WO
200202560	Jan 2002	WO
200214271	Feb 2002	WO
200224698	Mar 2002	WO
2002053516	Jul 2002	WO
2002068420	Sep 2002	WO
2003000241	Jan 2003	WO
2003000250	Jan 2003	WO
2003002531	Jan 2003	WO
2003002553	Jan 2003	WO
2003004496	Jan 2003	WO
2003006425	Jan 2003	WO
2003024965	Mar 2003	WO
2003033686	Apr 2003	WO
2003034944	May 2003	WO
2003035177	May 2003	WO
2003037327	May 2003	WO
2003053929	Jul 2003	WO
2003055881	Jul 2003	WO
2003057200	Jul 2003	WO
2003057245	Jul 2003	WO
2003059327	Jul 2003	WO
2003061688	Jul 2003	WO
2003064454	Aug 2003	WO
2003074500	Sep 2003	WO
2003088900	Oct 2003	WO
2003094909	Nov 2003	WO
2003099279	Dec 2003	WO
2003099836	Dec 2003	WO
2003104229	Dec 2003	WO
2003106428	Dec 2003	WO
2004002924	Jan 2004	WO
2004011416	Feb 2004	WO
2004016587	Feb 2004	WO
2000003735	Mar 2004	WO
2004018467	Mar 2004	WO
2004018468	Mar 2004	WO
2004018469	Mar 2004	WO
WO-2004018468	Mar 2004	WO
2004028524	Apr 2004	WO
2004033455	Apr 2004	WO
2004035575	Apr 2004	WO
2004037169	May 2004	WO
2004041820	May 2004	WO
2004043940	May 2004	WO
2004046148	Jun 2004	WO
2004048379	Jun 2004	WO
2004050658	Jun 2004	WO
2004052362	Jun 2004	WO
2004058233	Jul 2004	WO
2004062689	Jul 2004	WO
2004065380	Aug 2004	WO
2004074246	Sep 2004	WO
2004081006	Sep 2004	WO
2004082402	Sep 2004	WO
2004096806	Nov 2004	WO
2004096811	Nov 2004	WO
2004106279	Dec 2004	WO
2004108730	Dec 2004	WO
2004111051	Dec 2004	WO
2005000846	Jan 2005	WO
2005000848	Jan 2005	WO
2005007137	Jan 2005	WO
2005007647	Jan 2005	WO
2005007658	Jan 2005	WO
2005012288	Feb 2005	WO
2005016365	Feb 2005	WO
2005023179	Mar 2005	WO
2005049022	Jun 2005	WO
2005051950	Jun 2005	WO
2005058901	Jun 2005	WO
2005061489	Jul 2005	WO
2005063750	Jul 2005	WO
2005075410	Aug 2005	WO
2005082906	Sep 2005	WO
2005085246	Sep 2005	WO
2005092870	Oct 2005	WO
2005092877	Oct 2005	WO
2005095343	Oct 2005	WO
2005095381	Oct 2005	WO
2005097798	Oct 2005	WO
2005107730	Nov 2005	WO
2005116000	Dec 2005	WO
2005116014	Dec 2005	WO
2005117861	Dec 2005	WO
2005117948	Dec 2005	WO
2006005613	Jan 2006	WO
2006027204	Mar 2006	WO
2006029577	Mar 2006	WO
2006029769	Mar 2006	WO
2006036664	Apr 2006	WO
2006040625	Apr 2006	WO
2006041976	Apr 2006	WO
2006047248	May 2006	WO
2006048209	May 2006	WO
2006048427	May 2006	WO
2006068163	Jun 2006	WO
2006071078	Jul 2006	WO
2006076231	Jul 2006	WO
2006078593	Jul 2006	WO
2006083491	Aug 2006	WO
2006116157	Nov 2006	WO
2006129785	Dec 2006	WO
2006135693	Dec 2006	WO
2006137085	Dec 2006	WO
2007007173	Jan 2007	WO
2007014886	Feb 2007	WO
2007014895	Feb 2007	WO
2007017423	Feb 2007	WO
07035665	Mar 2007	WO
2007033350	Mar 2007	WO
2007035355	Mar 2007	WO
2007035665	Mar 2007	WO
2007038979	Apr 2007	WO
2007041053	Apr 2007	WO
2007050485	May 2007	WO
2007071738	Jun 2007	WO
2007072083	Jun 2007	WO
2007078726	Jul 2007	WO
2007093610	Aug 2007	WO
2007099345	Sep 2007	WO
2007120702	Oct 2007	WO
2007120936	Oct 2007	WO
2007128721	Nov 2007	WO
2007128724	Nov 2007	WO
2007128761	Nov 2007	WO
2007135196	Nov 2007	WO
2007136151	Nov 2007	WO
2007137107	Nov 2007	WO
2007147185	Dec 2007	WO
2007148185	Dec 2007	WO
2007149797	Dec 2007	WO
2003057245	Jan 2008	WO
2008005569	Jan 2008	WO
2008005576	Jan 2008	WO
2008017670	Feb 2008	WO
2008017670	Feb 2008	WO
2008022267	Feb 2008	WO
2008055870	May 2008	WO
2008055940	May 2008	WO
2008070692	Jun 2008	WO
2008077639	Jul 2008	WO
2008081205	Jul 2008	WO
2008083238	Jul 2008	WO
2008087198	Jul 2008	WO
2008093878	Aug 2008	WO
2008093882	Aug 2008	WO
2008097180	Aug 2008	WO
2008113000	Sep 2008	WO
2008130998	Oct 2008	WO
2008131149	Oct 2008	WO
2008137435	Nov 2008	WO
2009011451	Jan 2009	WO
2009022007	Feb 2009	WO
2009022008	Feb 2009	WO
2009022009	Feb 2009	WO
2009022010	Feb 2009	WO
2009024542	Feb 2009	WO
2009063072	May 2009	WO
2009091082	Jul 2009	WO
2009099734	Aug 2009	WO
2009111200	Sep 2009	WO
2009112691	Sep 2009	WO
2009121945	Oct 2009	WO
2009123992	Oct 2009	WO
2009147125	Dec 2009	WO
201092124	Feb 2010	WO
2010015664	Feb 2010	WO
2010018217	Feb 2010	WO
2010029089	Mar 2010	WO
2010043688	Apr 2010	WO
2010045656	Apr 2010	WO
2010072776	Jul 2010	WO
2010079197	Jul 2010	WO
2010086411	Aug 2010	WO
2010092125	Aug 2010	WO
2010092163	Aug 2010	WO
2010096384	Aug 2010	WO
2010106457	Sep 2010	WO
2010126908	Nov 2010	WO
2010140111	Dec 2010	WO
2010147768	Dec 2010	WO
2011011541	Jan 2011	WO
2011039337	Apr 2011	WO
2011039367	Apr 2011	WO
2011064352	Jun 2011	WO
2011109333	Sep 2011	WO
2011113947	Sep 2011	WO
2011138380	Nov 2011	WO
2011138421	Nov 2011	WO
2011154496	Dec 2011	WO
2011161161	Dec 2011	WO
2011163206	Dec 2011	WO
2012031124	Mar 2012	WO
2012039420	Mar 2012	WO
2012065993	May 2012	WO
2012088682	Jul 2012	WO
2012089127	Jul 2012	WO
2012106303	Aug 2012	WO
2012120040	Sep 2012	WO
2003061688	Apr 2013	WO
2013098372	Jul 2013	WO
2013103629	Jul 2013	WO
2013131967	Sep 2013	WO
2013171167	Nov 2013	WO
2013174768	Nov 2013	WO
2013179307	Dec 2013	WO
2014029848	Feb 2014	WO
2014140284	Sep 2014	WO
2014170383	Oct 2014	WO

Non-Patent Literature Citations (638)

Entry
Cygankiewicz, Andrzej et al., Investigations into the Piperazine Derivatives of Dimethylxanthine:, Acta Polon Pharm. [Papers of Polish Pharmacology], XXXOV, No. 5, pp. 607-612, 1977.
Dave, K.G. et al., “Reaction of Nitriles under Acidic Conditions, Part I. A General Method of Synthesis of Condensed Pyrimidines”, J. Heterocyclic Chemistry, BD, 17, 1, ISSN 0022-152X,Nov. 1980, p. 1497-1500.
Dave, Rutesh H. “Overview of pharmaceutical excipients used in tablets and capsules.” Drug Topics, Oct. 24, 2008.
Deacon, Carolyn F., et al., “Linagliptin, a xanthine based dipeptyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes” Expert Opinion Investig. Drugs 2010, 19 (1) p. 133-140.
Deacon, C.F. et al; “Dipeptidyl peptidase IV inhabitation as an approach to the treatment and prevention of type 2 diabetes: a historical perspective;” Biochemical and Biophysical Research Communications (BBRC) 294 (2002) 1-4.
Deacon, C.F., et al. Inhibitors of dipeptidyl peptidase IV: a novel approach for the prevention and treatment of Type 2 diabetes? Expert Opinion on Investigational Drugs, Sep. 2004, vol. 13, No. 9, p. 1091-1102.
Deacon, Carolyn F., “Dipeptidyl peptidase 4 inhibition with sitagliptin: a new therapy for Type 2 diabetes.” Expert Opinion on Investigational Drugs, 2007, vol. 16, No. 4, pp. 533-545.
Definition of “prevent”, e-dictionary, Aug. 15, 2013, http://dictionary.reference.com/browse/prevent.
DeMeester, I. et al; “CD26, let it cut or cut it down”, Review: Immunology Today; Aug. 1999, vol. 20, No. 8 pp. 367-375.
Demuth, H-U. et al., “Type 2 diabetes—Therapy with dipeptidyl peptidase IV inhibitors”. Biochimica et Biophysica Acta, vol. 1751(1), 2005, p. 33-44.
Diabetes Frontier, 2007, vol. 18, No. 2, p. 145-148.
Diabetes Health Center, “Diabetic Retinopathy—Prevention.” Retrieved online Mar. 22, 2011. www.diabetes.webmd.com/tc/diabetic-retinopathy-prevention <http://www.diabetes.webmd.com/td/diabetic-retinopathy-prevention?print=true>.
Diabetesincontrol.com “EASD: Eucreas, a Combination of Galvus and Metformin, Recommended for Approval.” Diabetes in Control.com, Sep. 25, 2007, Retrieved from internet on Nov. 30, 2012, http:/ /www.diabetesincontrol.com/articles/53-diabetes-news/5145.
Diabetic Neuropathy, Retrieved online Mar. 6, 2012. www.mayoclinic.com/health/diabetic-neuropathy/DS01045/METHOD=print&DSE <http://www.mayoclinic.com/health/diabetic-neuropathy/DS01045/METHOD=print&DSE>.
Dittberner, S. et al., “Determination of the absolute bioavailability of BI 1356, a substance with non-linear pharmacokinetics, using a population pharmacokinetic modeling approach.” Abstracts of the Annual Meeting of the Population Approach Group in Europe, 2007.
Drucker, Daniel J., “Dipeptidyl Peptidase-4 Inhibition and the Treatment of Type 2 Diabetes.” Diabetes Care, 2007, vol. 30, No. 6, pp. 1335-1343.
Drucker, et al.., The incretin system:glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet, 2006, 368: 1696-705.
Dugi, K. et al., “Safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 1356, a novel DPP-IV inhibitor with a wide therapeutic window.” Diabetic Medicine, 2006, vol. 23, Suppl. 4, p. 300.
Dugi, K.A. et al., “BI 1356, a novel xanthine-based DPP-IV inhibitor, exhibits high potency with a wide therapeutic window and significantly reduces postprandial glucose excursions after an oGTT”. Diabetologia, vol. 50, No. Suppl 1, Sep. 2007, p. S367, and 43rd Annual Meeting of the European Association for the Study of Diabetes; Amsterdam, Netherlands, Sep. 18-21, 2007.
Dunitz, J. et al., “Disappearing Polymorphs.” Acc. Chem. Res. 1995, vol. 28, No. 4, pp. 193-200.
Eckhardt Matthias et al: 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-yny 1-3-methyl-1-(4-methyl-quina zolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes: Journal of Medicinal Chemistry, American Chemical Society. Washington.; US, vol. 50, No. 26, Dec. 1, 2007, p. 6450-6453.
Eckhardt, M. et al., “3,5-dihydro-imidazo[4,5-d]pyridazin-4-ones: a class of potent DPP-4 inhibitors” Bioorganic & Medicinal Chemistry Letters, Pergamon, Elsevier Science, GB, vol. 18, No. 11, Jun. 1, 2008, pp. 3158-3162, XP022711188.
Edosada, C. Y. et al., “Selective Inhibition of Fibroblast Activation Protein Protease Based on Dipeptide Substrate Specificity.” The Journal of Biological Chemistry, 2006, vol. 281, No. 11, pp. 7437-7444.
Elrishi M A et al: “The dipeptidyl-peptidase-4 (D::-4) inhibitors: A new class of oral therapy for patients with type 2 diabetes mellitus” Practical Diabetes International Chichester, vol. 24, No. 9, Nov. 1, 2007 pp. 474-482.
EMEA Guidelines on Eucreas®, 2007, pp. 1-27.
EMEA Guidelines on Galvus®, 2007, pp. 1-34.
EMEA: European Medicines Agency, “Galvus (vildagliptin)” Retrieved online on Jan. 21, 2016.
EMEA: European Medicines Agency, ICH Topic E4, “Dose Response Information to Support Drug Registration.” 1994, pp. 1-10.
EU Clinical Trial Register, “A multicenter, international, rendomized, parallel group, double-blind, placebo-controlled, cardiovascular safety and renal microvascular outcome study with linagliptin, 5 mg once daily in patients with type 2 diabetes mellitus at high vascular risk.” Aug. 19, 2015.
Eucreas Scientific Discussion, 2007, p. 1-27, www.emea.europa.eu/humandocs/PD/Fs/EPAR/eucreas/H-807-en6.pdf, Anonymous.
European Search Report for EP 08 15 9141 dated Apr. 6, 2009 (European counterpart of U.S. Appl. No. 12/143,128).
Eyjolfsson, Reynir “Lisinopril-Lactose Incompatibility.” Drug Development and Industrial Pharmacy, 1998, vol. 24, No. 8, pp. 797-798.
Fantus, George, “Metformin's contraindications: needed for now.” Canadian Medical Association Journal, 2005, vol. 173, No. 5, pp. 505-507.
Feng, J. et al., “Discovery of Alogliptin: A Potent, Selective, Bioavailable, and Efficacious Inhibitor of Dipeptidyl Peptidase IV.” Journal of Medicinal Chemistry, 2007, vol. 50, No. 10, pp. 2297-2300.
Ferreira, L. et al., “Effects of Sitagliptin Treatment on Dysmetabolism, Inflammation, and Oxidative Stress in an Animal Model of Type 2 Diabetes (ZDF Rat).” Mediators of Inflammation, 2010, vol. 2010, pp. 1-11.
Ferry, Robert Jr., “Diabetes Causes.” eMedicine Health, MedicineNet.com, 2013, Retrieved from internet on Aug. 22, 2013,<http://www.onhealth.com/diabetes_health/page3.htm#diabetes_causes>.
Flatt, P.R. et al., “Dipeptidyl peptidase IV (DPP IV) and related molecules in type 2 diabetes.” Frontiers in Bioscience, 2008, vol. 13, pp. 3648-3660.
Florez, J. et al. “TCF7L2 Polymorphisms and Progression to Diabetes in the Diabetes Prevention Program.” The New England Journal of Medicine, 2006, vol. 355, No. 3, pp. 241-250.
Forst, T. et al., “The Novel, Potent, and Selective DPP-4 Inhibitor BI 1356 Significantly Lowers HbA1c after only 4 weeks of Treatment in Patients with Type 2 Diabetes.” Diabetes, Jun. 2007, Poster No. 0594P.
Forst, T. et al., “The oral DPP-4 inhibitor linagliptin significantly lowers HbA1c after 4 weeks of treatment in patients with type 2 diabetes mellitus.” Diabetes, Obesity and Metabolism, 2011, vol. 13, pp. 542-550.
Fukushima et al., Drug for Treating Type II Diabetes (6), “action-mechanism of DPP-IV inhibitor and the availability thereof” Mebio, 2009, vol. 26, No. 8, p. 50-58.
Gall, “Prevalence of micro-and macroalbuminuria, arterial hypertension, retinopathy and large vessel disease in European type 2 (non-insulin dependent) diabetic patients”, Diabetologia (1991) 655-661.
Gallwitz, B. “Sitagliptin with Metformin: Profile of a Combination for the Treatment of Type 2 Diabetes”. Drugs of Today, Oct. 2007, 43(10), p. 681-689.
Gallwitz, B. et al., “2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial.” Lancet, 2012, vol. 380, pp. 475-483.
Gallwitz, B. et al., “Saxagliptin, a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes”. IDRUGS, vol. 11, No. 12, Dec. 2008, p. 906-917.
Gallwitz, B. et al., DPP IV inhibitors for the Treatment of Type 2 Diabetes; Diabetes Frontier (2007) vol. 18, No. 6 pp. 636-642.
Gallwitz, B., “Safety and efficacy of linagliptin in type 2 diabetes patients with common renal and cardiovascular risk factors.” Therapeutic Advances in Endocrinology and Metabolism, 2013, vol. 4, No. 3, pp. 95-105.
Galvus (Vildagliptin) Scientific Discussion, EMEA, 2007, pp. 1-34.
Garber, A. J. et al., “Effects of Vildagliptin on Glucose Control in Patients with Type 2 Diabetes Inadequately Controlled with a Sulphonylurea”. Diabetes, Obesity and Metabolism (2008) vol. 10 pp. 1047-1055.
Garber, A.J. et al., “Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes.” Diabetes, Obesity and Metabolism, 2002, vol. 4, pp. 201-208.
Sathananthan, A., et al., “Personalized pharmacotherapy for type 2 diabetes mellitus”. Personalized Medicine 2009 Future Medicine Ltd, vol. 6, No. 4, Jul. 2009, p. 417-422.
Sauer, R, et al. “Water-soluble phosphate prodrugs of 1-Propargyl-7-styrylxanthine derivatives, A2A-selective adenosine receptor antagonists”. Journal Med. Chem., vol. 43, Issue 3, Jan. 2000, p. 440-448.
Schillinger, M. et al., “Restenosis after percutaneous angioplasty: the role of vascular inflammation.” Vascular Health and Risk Management, 2005, vol. 1, No. 1, pp. 73-78.
Schmidt, D. et al., “Fibromatosis of Infancy and Childhood Histology, Ultrastructure and Clinicopathologic Correlation.” Zeitschrift für Kinderchirurgie, 1985, vol. 40, No. 1, pp. 40-46.
Schnapp, G. et al., “Analysis of Binding Kinetics and Thermodynamics of DPP-4 Inhibitors and their Relationship to Structure.” 23rd PSDI, Protein Structure Determination in Industry, Tegernsee, Germany, Nov. 8-10, 2015.
Schnapp, G. et al., “Analysis of binding kinetics and thermodynamics of DPPIV Inhibitors and their relationship to structure.” International Workshop: The aspect of time in drug design, Schloss Rauischholzhausen, Marburg, Germany, Mar. 24-27, 2014.
Schnapp, G. et al., “Comparative Enzyme Kinetic Analysis of the Launched DPP-4 Inhibitors.” American Diabetes Association 74th Scientific Sessions, Poster 1048-P, 2014.
Schnapp, G. et al., “Comparative Enzyme Kinetic Analysis of the Launched DPP-4 Inhibitors.” American Diabetes Association, Abstract 1048-P, 2014.
Schurmann, C. et al., “The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Attenuates Inflammation and Accelerates Epithelialization in Wounds of Diabetic ob/ob Mice.” The Journal of Pharmacology and Experimental Therapeutics, 2012, vol. 342, No. 1, pp. 71-80.
Schwartz, M. S. et al., “Type 2 Diabetes Mellitus in Childhood: Obesity and Insulin Resistance”. JAOA Review Article, vol. 108, No. 9, Sep. 2008, p. 518.
Scientific Discussion, EMEA, Pramipexole, 2005, pp. 1-10.
Scientific Discussion: “Eucreas. Scientific discussion”. Online Oct. 2007, p. 1-27, URL:http://www.emea.europa.eu/humandocs/PDFs/EPAR/eucreas/H-807-en6.pdf. see point 2. quality aspects pp. 2-4. (EMEA).
Sedo, A. et al; “Dipeptidyl peptidase IV activity and/or structure homologs: Contributing factors in the pathogenesis of rheumatoid arthritis?” Arthritis Research & Therapy 2005, vol. 7, pp. 253-269.
Shanks, N. et al., Are animal models predictive for humans?, PEHM, Philosophy, Ethics, and Humanaities in Medicine, 4(2), 2009, 1-20.
Sharkovska, Y., et al., “DPP-4 Inhibition with Linagliptin Delays the Progression of Diabetic Nephropathy in db/db Mice.” 48th EASD Annual Meeting, Berlin, Abstract 35, Oct. 2012.
Sheperd, Todd M. et al., “Efective management of obesity.” The Journal of Family Practice, 2003, vol. 52, No. 1, pp. 34-42.
Shintani, Maki, et al., “Insulin Resistance and Genes” Circulatory Sciences (1997) vol. 17, No. 12 pp. 1186-1188.
Shu, L. et al., “Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function.” Human Molecular Genetics, 2009, vol. 18, No. 13, pp. 2388-2399.
Shu, L. et al., “Transcription Factor 7-Like 2 Regulates B-Cell Survival and Function in Human Pancreatic Islets.” Diabetes, 2008, vol. 57, pp. 645-653.
Silverman, G. et al., “Handbook of Grignard Reagents.” 1996, Retrieved online: <http://books.google.com/books?id=82CaxfY-uNkC&printsec=frontcover&dq=intitle:Handbook+intitle:of+intitle:Grignard+intitle: Reagents&hl=en&sa=X&ei=g06GU5SdOKngsATphYCgCg&ved=0CDYQ6AEwAA#v=onepage&q&f=false>.
Singhal, D. et al., “Drug polymorphism and dosage form design: a practical perspective.” Advanced Drug Delivery Reviews, 2004, vol. 56, pp. 335-347.
Sortino, M.A. et al., “Linagliptin: a thorough characterization beyond its clinical efficacy.” Frontiers in Endocrinology, 2013, vol. 4, Article 16, pp. 1-9.
St. John Providence Health Center, “Preventing Obesity in Children and Teens.” Retrieved from internet on Aug. 22, 2013, http://www.stjohnprovidence.org/Health I nfoLib/swarticle.aspx?type=85&id= P07863.
Stahl, P.H., “Handbook of Pharmaceutical Salts” C.G. Wermuth, Wiley-VCH, 2002, pp. 1-374.
Standl, E. et al., “Diabetes and the Heart.” Diabetes Guidelines (DDG), 2002, pp. 1-25.
Sulkin, T.V. et al., “Contraindications to Metformin Therapy in Patients With NIDDM.” Diabetes Care, 1997, vol. 20, No. 6, pp. 925-928.
Sune Negre, J. M. “New Galenic Contributions to Administration Forms”. Continued Training for Hospital Pharmacists 3.2., (Publication date unavailable), Retrieved from internet on Feb. 23, 2011, http://www.ub.es/legmh/capitols/sunyenegre.pdf.
Suzuki, Y. et al., “Carbon-Carbon Bond Cleavage of a-Hydroxybenzylheteroarenes Catalyzed by Cyanide Ion: Retro-Benzoin Condensation Affords Ketones and Heteroarenes and Benzyl Migration Affords Benzylheteroarenes and Arenecarbaldehydes.” Chemical Pharmaceutical Bulletin, 1998, vol. 46(2), pp. 199-206.
Tadayyon, M. et al., “Insulin sensitisation in the treatment of Type 2 diabetes.” Expert Opinion Investigative Drugs, 2003, vol. 12, No. 3, pp. 307-324.
Takai, S. et al., “Significance of Vascular Dipeptidyl Peptidase-4 Inhibition on Vascular Protection in Zucker Diabetic Fatty Rats.” Journal of Pharmacological Sciences, 2014, vol. 125, pp. 386-393.
Takeda Press Release: “Voglibose (BASEN) for the prevention of type 2 diabetes mellitus: A Randomized, Double-blind Trial in Japanese Subjects with Impaired Glucose Tolerance.” 2008, Retrieved online Jul. 6, 2015. https://www.takeda.com/news/2008/20080526_3621.html.
Tamm, E, et al., “Double-blind study comparing the immunogenicity of a licensed DTwPHib-CRM197 conjugate vaccine (Quattvaxem TM) with three investigational, liquid formulations using lower doses of Hib-CRM197 conjugate”. Science Direct, Vaccine, Feb. 2005, vol. 23, No. 14, p. 1715-1719.
Tanaka, S.. et al; “Suppression of Arthritis by the Inhibitors of Dipeptidyl Peptidase IV,” In. J. Immunopharmac., vol. 19, No. 1, pp. 15-24, 1997.
Targher, G. et al., “Prevalence of Nonalcoholic Fatty Liver Disease and Its Association With Cardiovascular Disease Among Type 2 Diabetic Patients.” Diabetes Care, 2007, vol. 30, No. 5, pp. 1212-1218.
Taskinen, M.-R. et al., “Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study.” Diabetes, Obesity and Metabolism, 2011, vol. 13, pp. 65-74.
Third Party Observation for application No. EP20070728655, May 13, 2013.
Thomas, L. et al, “BI 1356, a novel and selective xanthine beased DPP-IV inhibitor, exhibits a superior profile when compared to sitagliptin and vildagliptin.” Diabetologia, 2007, vol. 50, No. Suppl. 1, p. S363.
Thomas, L., “Chronic treatment with the Dipeptidyl Peptidase-4 Inhibitor BI 1356[9R)-8-(3-Amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione] Increases Basal Glucagon-Like Peptide-1 and Improves Glycemic Control in Diabetic Rodent Models” The Journal of Pharmacology and Experimental Therapeutics, Feb. 2009, vol. 328, No. 2, pp. 556-563.
Thomas, Leo et al: “(R)-8-(3-Amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1- (4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a Novel Xanthine-Based Dipeptidyl Peptidase 4 Inhibitor . . . ” Journal of Pharmacology and Experimental Therapeutics, 2008, vol. 325, No. 1, pp. 177.
Thornber, C.W., “Isosterism and Molecular Modification in Drug Design.” Chemical Society Reviews, 1979, pp. 563-580.
Tounyoubyou, “Symposium-19: Future Perspectives on Incretion Therapy in Diabetes.” 2008, vol. 51, Suppl. 1, p. S-71, S19-2.
Tradjenta, Highlights of Prescribing Information (revised Sep. 2012).
Tribulova, N. et al. “Chronic Disturbances in NO Production Results in Histochemical and Subcellular Alterations of the Rat Heart.” Physiol. Res., 2000, vol. 49, No. 1, pp. 77-88.
Tsujihata, et al., “TAK-875, an orally available G protein-Coupled receptor 40/Free fatty acid receptor 1 Agonist, Enhances Glucose Dependent Insulin Secretion and improves both Postprandial and Fasting hyperglycemic in type 2 Diabetic rats”, J. Pharm Exp. 2011, vol. 339, No. 1, p. 228-237.
Tsuprykov, O. et al., Linagliptin is as Efficacious as Telmisartan in Preventing Renal Disease Progression in Rats with 5/6 Nephrectomy, 73rd Annual Meeting Science Session, ADA, Chicago, Jun. 2013.
Turner, R.C. et al., “Glycemic Control With Diet, Sulfonylurea, Metformin, or Insulin in Patients With Type 2 Diabetes Mellitus Progressive Requirement for Multiple Therapies (UKPDS 49)” The Journal of the American Medical Association, 1999, vol. 281, No. 21, pp. 2005-2012.
U.S. Appl. No. 15/235,575, filed Aug. 12, 2016, Inventor: Klaus DUGI. (The cited pending U.S. application is stored in the USPTO IFW system (MPEP 609.04(a)(II)(C)).
Uhlig-Laske, B. et al., “Linagliptin, a Potent and Selective DPP-4 Inhibitior, is Safe and Efficacious in Patients with Inadequately Controlled Type 2 Diabetes Despite Metformin Therapy”. 535-P Clinical Therapeutics/New Technology—Pharmacologic Treatment of Diabetes or Its Complications, Posters, vol. 58, Jun. 5, 2009, p. A143.
United Healthcare, “Diabetes.” Retrieved from internet on Aug. 22, 2013, http://www.uhc.com/source4women/health_topics/diabetesirelatedinformation/dOf0417b073bf11OVgnVCM1000002f1Ob1Oa_.htm.
Van Reek, M. et al., “Ezetimibe, a Potent Cholesterol Absorption Inhibitor, Normalizes Combined Dyslipidemia in Obese Hyperinsulinemic Hamsters.” Diabetes, 2001, vol. 50, pp. 1330-1335.
Falanga, Lancet, Wound healing and impairment in the diabetic foot, vol. 366, 2005.
Who drug information, International nonproprietary Names for Pharmaceutical Substances, vol. 23, 2009.
Thielitz, Inhibitors of Dipeptidyl Peptidase IV and aminopeptidase N target Major Pathogenetic steps in Acne initiation, Journal of inventigative Dermatology, 2007.
Rai, Effect of Glycemic Control on apoptosis in diabetic wounds, Journal of Wound care, vol. 14, 2005.
Mcintosh, Dipeptidyl Synthase IV inhibitors, Regulatory Peptides, vol. 128, 2005.
Kaji, Dipeptidyl peptidase-4 inhibitor attenuates hepatic fibrosis via suppression of activated hepatic stellate cell in rats, J. Gastro, 2012.
Gorrell, Fibroblast Activation Protein, Handbook of Proteolytic Enzymes, 3rd ed., 2013.
McIennan, Molecular aspects of wound healing in diabetes, Dept. of Endocrinology, Univ of Sydney, vol. 14, 2006.
Pradham, Wound-healing abnormalities in Diabetes, Dept. of surgertm Harvard, Touch Briefings, 2007.
FDA Drug Safety Communication, FDA revises warnings regarding diabetes medicine metformin in certain patients with reduced kidney function, Apr. 8, 2016.
Groop, Diabetologica, 2012, vol. 55.
Basi, Diabetes Care, vol. 31, 2008.
Donnelly, BMJ, Vascular complications of diabetes, 2000.
Kendall, Emerging Treatments in Diabetes Care, Effects of Exenatide on Glycemic Control over 30 weeks in Patients with Type 2 Diabetes, vol. 28, 2005.
Sampanis, Hippokratia, Management of HypergIcemia in patients with diabetes mellitus and chronic renal failure, vol. 12, p. 22-27, 2008.
Hasanato, Diagnostic Efficacy of random albumin creatinine ration, Saudi Med, J., 2016, vol. 37.
Forst, The oral DPP 4 inhibitor linagliptin significantly lowers HbA1c after 4 weeks of treatment in patients with diabetes, Diabetes Obes Metab, vol. 13, 2011.
Garber, A.J. et al., “Update: Vildaglitin for the treatment of Type 2 diabetes” Expert Opinion on Investigational Drugs, 200801GB, vol. 17, No. 1, Jan. 2008, p. 105-113.
Garcia-Soria, et al., “The dipeptidyl peptidase-4 inhibitor PHX1149 improves blood glucose control in patents with type 2 diabetes mellitus”. Diabetes, Obesity and Metabolism, Apr. 2008, vol. 10, No. 4, p. 293-300.
Geka, 2001, vol. 67, No. 11, p. 1295-1299.
Gennaro, Alfonso R. Remington Farmacia, 2003, Spanish copy: p. 828, English copy: pp. 711-712, Preformulation, Chapter 38.
Gennaro, Alfonso R., Remington Farmacia, 19th Edition, Spanish copy, 1995, p. 2470.
Gennaro, Alfonso, R; Remington: The Science and Practice of Pharmacy: Oral Solid Dosage Forms; Mack Publishing Company, Philadelphia, PA (1995) vol. II, 19th Edition, Ch. 92 pp. 1615-1649.
Gennaro, Alfonso; Remington: The Science and Practice of Pharmacy, Twentieth Edition, 2000, Chapter 45, pp. 860-869.
Giron, D.; Thermal Analysis and Calorimetric Methods in the Characterisation of Polymorphs and Solvates; Thermochimica Acta (1995) vol. 248 pp. 1-59.
GLUCOPHAGE® Prescribing Information, 2001.
Glucotrol XL (glipizide), package insert, Pfizer, Apr. 1, 2002.
Goldstein, L.A., et al., “Molecular cloning of seprase: a serine integral membrane protease from human melanoma.” Biochimica et Biophysica Acta, vol. 1361, 1997, No. 1, pp. 11-19.
Gomez-Perez, et al, “Insulin Therapy:current alternatives”, Arch. Med.Res. 36: p. 258-272 (2005).
Goodarzi, M.O. et al., “Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents.” Diabetes, Obesity and Metabolism, 2005, vol. 7, pp. 654-665.
Graefe-Mody et al., “The novel DPP-4 inhibitor BI 1356 (proposed tradename ONDERO) and Metformin can be Safely Co-administered Without Dose Adjustment.” Poster No. 553-P ADA Jun. 6-10, 2008, San Francisco http://professional.diabetes.org/content/posters/2008/p553-p. pdf.
Graefe-Mody, et al; Evaluation of the Potential for Steady-State Pharmacokinetic and Phamacodynamic Interactions Between the DPP-4 Inhibitor Linagliptin and Metformin in Healthy Subjects; Currents Medical Research and Opinion (2009) vol. 25, No. 8 pp. 1963-1972.
Graefe-Mody, U. et al.,0 “Effect of Renal Impairment on the Pharmacokinetics of the Dipeptidyl Peptidase-4 Inhibitor Linagliptin.” Diabetes, Obseity and Metabolism, 2011, pp. 939-946.
Greene, T.W., et al., “Protection for the Amino Group”. Protective Groups in Organic Synthesis, 3rd edition, 1999, p. 494-653.
Greischel, et al., Drug Metabolism and Deposition, “The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Exhibits Time- and Dpse-Dependent Localization in Kidney, Liver, and Intestine after Intravenous Dosing: Results from High Resolution Autoradiography in Rats”, 2010, vol. 38, No. 9, p. 1443-1448.
Groop, P.-H. et al., “Effects of the DPP-4 Inhibitor Linagliptin on Albuminuria in Patients with Type 2 Diabetes and Diabetic Nephropathy” 48th EASD Annual Meeting, Berlin, Abstract 36, Oct. 2012.
Guglielmi, C. et al., “Latent autoimmune diabetes in the adults (LADA) in Asia: from pathogenesis and epidemiology to therapy.” Diabetes/Metabolism Research and Reviews, 2012, vol. 28, Supplement 2, pp. 40-46.
Gupta, V. et al., “Choosing a Gliptin.” Indian Journal of Endocrinology and Metabolism, 2011, vol. 15, No. 4, pp. 298-308.
Gwaltney, S. “Medicinal Chemistry Approaches to the Inhibition of Dipeptidyl Peptidase IV”, Current Topics in Medicinal Chemistry, 2008, 8, p. 1545-1552.
Gwaltney, S.L. II et al., “Inhibitors of Dipeptidyl Peptidase 4.” Annual Reports in Medicinal Chemistry, 2005, vol. 40, pp. 149-165.
Hainer, Vojtech MD, PHD “Comparative Efficiency and Safety of Pharmacological Approaches to the Management of Obesity.” Diabetes Care, 2011, vol. 34, Suppl. 2, pp. S349-S354.
Halimi, “Combination treatment in the management of type 2 diabetes: focus on vildagliptin and metformin as a single tablet”, Vascular Health and Risk Management, 2008 481-92.
Halimi, S. et al., “Combination treatment in the management of type 2 diabetes: focus on vildagliptin and metformin as a single tablet.” Vascular Health and Risk Management, 2008, vol. 4, No. 3, pp. 481-492.
Haluzik, M. et al., “Renal Effects of DPP-4 Inhibitors: A Focus on Microalbuminuria.” International Journal of Endocrinology, 2013, vol. 35, No. 6, pp. 1-7.
Hammouda, Y. et al., “Lactose-induced Discoloration of Amino Drugs in Solid Dosage Form.” Die Pharmazie, 1971, vol. 26, p. 181.
Hansen, H. et al., “Co-Administration of the DPP-4 Inhibitor Linagliptin and Native GLP-1 Induce Body Weight Loss and Appetite Suppression.” 73rd Annual Meeting Science Session, ADA, Chicago, Jun. 21, 2013.
Hashida, Mitsuru, “Strategies for designing and developing oral administration formulations.” Yakuji-Jiho, Inc., 1995, pp. 50-51.
Hayashi, Michio., “Recipe for Oral Hypoglycemic Agents to Pathological Condition” Pharmacy (2006) vol. 57, No. 9 pp. 2735-2739.
He, Y. L. et al., “Bioequivalence of Vildagliptin/Metformin Combination Tablets and Coadministration of Vildagliptin and Metforming as Free Combination in Healthy Subjects”. J. Clinical Pharmacology, 2007, vol. 47, No. 9, Abstracts of the 36th Annual Meeting of the American College of Clinical Pharmacology, San Francisco, CA, Abstract 116, p. 1210.
He, Y.L. et al., “The influence of hepatic impariment on the pharmacokinetics f the dipeptidyl peptidase IV (DPP-4)Inhibitor vildagliptin” European Journal of Clinical Pharmacology, vol. 63, No. 7, May 8, 2007, p. 677-686.
He, Y.L. et al., “The Influence of Renal Impairment on the Pharmacokinetics of Vildagliptin.” Clinical Pharmacology & Therapeutics, 2007, vol. 81, Suppl. 1, Abstract No. PIII-86.
Headland, K. et al., “The Effect of Combination Linagliptin and Voglibose on Glucose Control and Body Weight.” 73rd Annual Meeting Science Session, ADA, Chicago, Jun. 21, 2013.
Heihachiro, A. et al., “Synthesis of Prolyl Endopeptidase Inhibitors and Evaluation of Their Structure-Activity Relationships: In Vitro Inhibition of Prolyl Endopeptidase from Canine Brain.” 1993, Chemical and Pharmaceutical Bulletin, vol. 41, pp. 1583-1588.
Heise, et al., Diabetes, Obesity and Metabolism, “Pharmacokinetics, pharmacokinetics and tolerability of mutilple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients”, 2009, vol. 11, No. 8, p. 786-794.
Heise, T. et al., “Treatment with BI 1356, a Novel and Potent DPP-IV Inhibitor, Significantly Reduces Glucose Excursions after an oGTT in Patients with Type 2 Diabetes.” A Journal of the American Diabetes Association, Jun. 2007, vol. 56, Supplement 1, Poster No. 0588P.
Herman, G. A. et al., “Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Type 2 Diabetes: Focus on Sitagliptin.” Cinical Pharmacology and Therapeutics, 2007, vol. 81, No. 5, pp. 761-767.
Herman, Gary et al. “Co-Administration of MK-0431 and Metformin in Patients with Type 2 Diabetes Does Not Alter the Pharmacokinetics of MK-0431 or Metformin” (2005) Journal of American Diabetes Association vol. 54, Supplement 1, 3 pgs.
Hermann, Robert, et al; Lack of Association of PAX4 Gene with Type 1 Diabetes in the Hungarian Populations; Diabetes (2005) vol. 54 pp. 2816-2819.
Hermansen, K., “Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor, Sitagliptin, in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Glimepiride Alone or on Glimepiride and Metformin”. Diabetes, Obesity and Metabolism (2007) vol. 9, No. 5 pp. 733-745.
Hilfiker, R. et al., “Relevance of Solid-state Properties for Pharmaceutical Products.” Polymorphism in the Pharmaceutical Industry, 2006, Chapter 1, pp. 1-19.
Hinke, S.A. et al., “Metformin Effects on Dipeptidylpeptidase IV Degradation of Glucagon-like Peptide-1.” Biochemical and Biophysical Research Communications, 2002, vol. 291, No. 5, pp. 1302-1308.
Hinke, S.A. et al., “On Combination Therapy of Diabetes With Metformin and Dipeptidyl Peptidase IV Inhibitors.” Diabetes Care, 2002, vol. 25, No. 8, pp. 1490-1492.
Hinnen, D. et al., “Incretin Mimetics and DPP-IV Inhibitors: New Paradigms for the Treatment of Type 2 Diabetes.” Journal of The American Board of Family Medicine, 2006, vol. 19, No. 6, pp. 612-620.
Hocher, B. et al., “Renal and Cardiac Effects of DPP-4 Inhibitors—from Preclinical Development to Clinical Research.” Kidney & Blood Pressue Research, 2012, vol. 36, No. 1, pp. 65-84.
Hocher, B. et al., “The novel DPP-4 inhibitors linagliptin and BI 14361 reduce infarct size after myocardial ischemia/reperfusion in rats.” International Journal of Cardiology, 2013, vol. 167, pp. 87-93.
Holman, et al., “Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes”, N. England Journal Medicine, p. 1716-1730, 2007.
Horsford, E. N. “On the source of free hydrochloric acid in the gastric juice.” Proceedings of the Royal Society of London, Published in 1868-1869, vol. 17, pp. 391-395.
International Search Report for PCT/EP2010/064691 dated Jan. 20, 2011.
International Search Report for PCT/EP2013/060309 dated Aug. 9, 2013.
International Search Report for PCT/EP2013/070979 dated Nov. 26, 2013.
International Search Report for PCT/EP2014/060160 dated Nov. 8, 2014.
Inukai, T., “Treatment of Diabetes in Patients for Whom Metformin Treatment is Not Appropriate.” Modem Physician, 2008, vol. 28, No. 2, pp. 163-165.
Inzucchi, Silvio E., “Oral Antihyperglycemic Therapy for Type 2 Diabetes.” The Journal of the American Medical Association, 2002, vol. 287, No. 3, pp. 360-372.
Isomaa, B. et al., “Cardiovascular Morbidity and Mortality Associated With the Metabolic Syndrome.” Diabetes Care, 2001, vol. 24, No. 4, pp. 683-689.
Iwamoto, Yasuhiko, “Insulin Glargine.” Nippon Rinsho, 2002, vol. 60, Suppl. 9, pp. 503-515.
Janumet Prescribing Information, revised Jan. 2008.
Januvia Medication Guide, 2010.
Januvia Prescribing Information and Product Label, 2006.
Januvia, 25mg, 50mg, 100 mg, Summary of Product Characteristics, 2015, www.medicines.org.uk/EMC <http://www.medicines.org.uk/EMC>.
Johansen, O. E. et al., “Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme.” Cardiovascular Diabetology, Biomed Central, 2012, vol. 11, No. 3, pp. 1-10.
Johansen, O.E. et al., “b-cell Function in Latnet Autoimmune Diabetes in Adults (LADA) Treated with Linagliptin Versus Glimepiride: Exploratory Results from a Two Year Double-Blind, Randomized, Controlled Study.” www.abstractsonline.com, Jun. 10, 2012, XP-002708003.
John Hopkins Children's Center, “Liver Disorders and Diseases.” Retrieved online May 26, 2014 <http://www.hopkinschildrens.org/non-alcoholic-fatty-liver-disease.aspx>.
Jones, R.M. et al., “GPR119 agonists for the treatment of type 2 diabetes”. Expert Opinion on Therapeutic Patents 2009 Informa Healthcare for GBR LNKSD—DOI: 10.1517/13543770903153878, vol. 19, No. 10, Oct. 2009, p. 1339-1359.
Kanada, S. et al., “Safety, tolerability, pharmacokenetics and pharmacodynamics of multiple doses of BI 1356 (proposed tradename ONDERO), a dipeptidyl peptidase 4 inhibitor, in Japanese patients with type 2 diabetes” Diabetes, vol. 57, No. Suppl. 1, Jun. 2008, p. A158-A159 and 68th Annual Meeting of the American Diabetes Association: San Francisco, CA , Jun. 6-10, 2008.
Kelly. T., “Fibroblast activation protein-cx and dipeptidyl peptidase IV (CD26)P: Cell-surface proteases that activate cell signaling and are potential targets for cancern therapy”. Drug Resistence Update 8, 2005, vol. 8. No. 1-2, pp. 51-58.
Kendall, D. M. et al., “Incretin Mimetics and Dipeptidyl Peptidase-IV Inhibitors: A Review of Emerging Therapies for Type 2 Diabetes.” Diabetes Technology & Therapeutics, 2006, vol. 8, No. 3, pp. 385-398.
Kharkevich, D. A., “Educational Literature” Pharmacology (1987) Third Edition, Meditsina Press, Moscow pp. 47-48.
Kibbe, A., Editor. Handbook of Pharmaceutical Excipients, Third Edition, Copovidon—pp. 196-197, Date of Revision: Dec. 16, 2008. Mannitol—pp. 424-425, Date of Revision: Feb. 19, 2009, Published in 2009.
Kidney Disease (Nephropathy), Retrieved online May 13, 2013. www.diabetes.org/living-with-diabetes/complications/kidney-disease-nephropathy.html <http://www.diabetes.org/living-with-diabetes/complications/kidney-disease-nephropathy.html>.
Kim, D. et al., “(2R)-4-Oxo-4-(3-(Trifluoremethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: A Potent, Orally Active Dipeptidyl Peptidase IV inhibitor for the Treatment of Type 2 Diabetes.” Journal Med. Chem, 2005, 48, p. 141-151.
Kim, Kwang-Rok et al., “KR-62436, 6-{2-{2-(5-cyano4,5-dihydropyrazol-1-yl)-2-oxoethylamino}ethylamino} nicotinonitrile, is a novel dipeptidyl peptidase-IV (DDP-IV inhibitor with anti-hyperglycemic activity” European Journal of Pharmacology 518, 2005, p. 63-70.
Kiraly, K. et al., “The dipeptidyl peptidase IV (CD26, EC 3.4.14.5) inhibitor vildagliptin is a potent antihyperalgesic in rats by promoting endomorphin-2 generation in the spinal cord.” European Journal of Pharmacology, 2011, vol. 650, pp. 195-199.
Kirpichnikov, D. et al., “Metformin: An Update.” Annals of Internal Medicine, 2002, vol. 137, No. 1, pp. 25-33.
Kishore, Preeti MD., “Complications of Diabetes Mellitus.” Merck Manual Consumer Version, 2016, pp. 1-7.
Klein, T. et al., “Linagliptin alleviates hepatic steatosis and inflammation in a mouse model of non-alcoholic steatohepatitis.” Medical Molecular Morphology, 2014, vol. 47, pp. 137-149.
Knorr, M. et al., “Comparison of Direct and Indirect Antioxidant Effects of Linagliptin (BI 1356, Ondero) with other Gliptins—Evidence for Anti-Inflammatory Properties of Linagliptin”. Free Radical Biology and medicine, Elsevier Science, U.S. vol. 49, Oct. 23, 2010, p. S197.
Knowler, W.C. et al., “Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin.” The New England Journal of Medicine, 2002, vol. 346, No. 6, pp. 393-403.
Komori, Kiyoshi., “Treatment of Diabetes in Patients for Whom Metforming Treatment is Not Appropriate” Modern Physician (2008) vol. 28, No. 2 pp. 163-165.
Konstantinou, D. M. et al., “Pathophysiology-based novel pharmacotherapy for heart failure with preserved ejection fraction.” Pharmacology & Therapeutics, 2013, vol. 140, No. 2, pp. 156-166.
Korom, S. et al; Inhibition of CD26/dipeptidyl peptidase IV activity in vivo prolongs cardiac allograft survival in rat recipients1,2, Transplantation, May 27, 1997, vol. 63, No. 10, pp. 1495-1500.
Kroller-Scön, S. et al., “Glucose-independent Improvement of Vascular Dysfunction in Experimental Sepsis by Dipeptidyl Peptidase-4 Inhibition.” Cardiovascular Research, 2012, vol. 96, No. 1, pp. 140-149.
Kumar, V. et al., “Maillard Reaction and Drug Stability.” Maillard Reactions in Chemistry, Food, and Health, 1994, No. 151, pp. 20-27.
Kuno, Y. et al., “Effect of the type of lubricant on the characteristics of orally disintegrating tablets manufactured using the phase transition of sugar alcohol.” European Journal of Pharmaceutics and Biopharmaceutics, 2008, vol. 69, pp. 986-992.
Lachman, L. et al., “The Theory and Practice of Industrial Pharmacy.” Varghese Publishing House, Third Edition, 1987, pp. 190-194.
Lakatos, P. L. et al., “Elevated Serum Dipeptidyl IV (CD26, EC 3.4.14.5) Activity in Experimental Liver Cirrhosis.” European Journal of Clinical Investigation, 2000, vol. 30, No. 9, pp. 793-797.
Lakatos, P. L. et al., “Elevated serum dipeptidyl peptidase IV (CD26, EC 3.4.14.5) activity in patients with primary biliary cirrhosis.” Journal of Hepatol, 1999, vol. 30, p. 740.
Lambier, A.M. et al., Dipeptidyl-Peptidase IV from Bench to Bedside: An Update on Structural Properties, Functions, and Clinical Aspects of the Enzyme DPP IV. Critical Reviews in Clinical Laboratory Sciences, 2003, 40(3), p. 209-294.
Lee Jones, K. et al., “Effect of Metformin in Pediatric Patients With Type 2 Diabetes.” Diabetes Care, 2002, vol. 25, No. 1, pp. 89-94.
Leibovitz, E. et al., “Sitagliptin pretreatment in diabetes patients presenting with acute coronary syndrome: results from the Acute Coronary Syndrome Israeli Survey (ACSIS).” Cardiovascular Diabetology, 2013, vol. 12, No. 1, pp. 1-7.
Levien,T.L. et al, “New drugs in development for the treatment of diabetes”, Diabetes Spectrum, American Diabetes Association, US, vol. 22, No. 2, Jan. 1, 2009, pp. 92-106.
Lieberman, H. et al., “Pharmaceutical Dosage Forms.” Marcel Dekker, Inc., 1980, vol. 1, p. 38.
Lim, S. et al., “Effect of a Dipeptidyl Peptidase-IV Inhibitor, Des-Fluoro-Sitagliptin, on Neointimal Formation after Balloon Injury in Rats.” Plos One, 2012, vol. 7, No. 4, pp. 1-11.
Linagliptin Monograph, Published by VACO PBM-SHG US Veteran's Administration, 2011, pp. 1-17.
Lindsay, J.R. et al., “Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes.” Diabetic Medicine, 2005, vol. 22, pp. 654-657.
Lovshin, J.A. et al., “Incretin-based therapies for type 2 diabetes mellitus.” Nature Reviews Endocrinology, 2009, vol. 5, pp. 262-269.
Lu, “High prevlaence of albuminuria in population based patients diagnosed with type 2 diabetes in the Shanghai downtown”, Diabestes Research and Clinical Practice (2007) 184-192.
Lyssenko, V. et al., “Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes.” The Journal of Clinical Investigation, 2007, vol. 117, No. 8, pp. 2155-2163.
Bundgaard, H. “Design of prodrugs: Bioreversible derivatives for various functional groups and chemical entities”. Royal Danish School of Pharmacy, 1985, p. 1-92.
Busso et al., “Circulating CD26 is Negatively Associated with Inflammation in Human and Experimental Arthritis,” Am. J. Path., vol. 166, No. 2, Feb. 2005, pp. 433-442.
Byrn, Stephen R. “Solid-State Chemistry of Drugs.” Academic Press, 1982, pp. 1-27.
Caira, M.R., “Crystalline polymorphism of organic compounds” Topics in Current Chemistry, Springer, Berlin, vol. 198, 1998, p. 163-208.
Campbell, R. Keith “Rationale for Dipeptidyl Peptidase 4 Inhibitors: A New Class of Oral Agents for the Treatment of Type 2 Diabetes Mellitus.” The Annals of Pharmacotherapy, Jan. 2007, vol. 41, pp. 51-60.
Canadian Diabetes Association, “Pharmacologic Management of Type 2 Diabetes.” Canadian Journal of Diabetes, 2003, vol. 27, Suppl. 2, pp. S37-S42.
Canadian Pharmacists Association, Compendium of Pharmaceuticals and Specialties, “Zestril” 2004, pp. 2289-2293.
Cao, C. et al., “The clinical application of linagliptin in Asians.” Therapeutics and Clinical Risk Management, 2015, vol. 11, pp. 1409-1419.
Castello, R. et al., “Discoloration of Tablets Containing Amines and Lactose.” Journal of Pharmaceutical Sciences, 1962, vol. 51, No. 2, pp. 106-108.
Chan, J.C. et al., “Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency.” 2008, Diabetes, Obesity and Metabolism, vol. 10, pp. 545-555.
Charbonnel, B. et al., “Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Added to Ongoing Metformin Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Alone.” Diabetes Care, 2006, vol. 29, No. 12, pp. 2638-2643.
Chaykovska, L. et al., “Effects of DPP-4 Inhibitors on the Heart in a Rat Model of Uremic Cardiomyopathy.” www.plosone.org, 2011, vol. 6, No. 11, p. e27861.
ChemGaroo, “Leaving Group.” 1999, Retrieved online: http://www.chemgapedia.de/vsengine/vlu/vsc/en/ch/12/oc/vluorganik/substitution/sn_2/sn 2. vlu/Page/vsc/en/ch/12/oc/substitution/sn_2/abgangsgrupen/abgangsgruppe. vscml. html.
Chemical Abstract. EP412358, 1991:185517, Findeisen.
Chemical Abstract: FR2707641, 1995:543545, Dodey.
Chemical Abstract: No. 211513-37-0—Dalcetrapib. “Propanethioic acid, 2-methyl-,S-(2-[[[1-(2-ethylbutyl)cyclohexyl}carbonyl}amino}pheyl}ester”. Formula: C23 H35 N O2 S. American Chemical Society. Sep. 20, 1998.
Chemical Abstract: No. 875446-37-0—Anacetrapib. “2-Oxazolidinone, 5-[3,5-bis(trifluoromethyl)phenyl]-3[[4′fluoro-2′-methoxy-5′-(1-methylethyl)-4-(trifluoromethyl)[1,1′-biphenyl]-2-yl]methyl]-4-methyl-,(4S,5R)-” Formula: C30 H25 F10 N O3. American Chemical Society, Feb. 28, 2006.
Chemical Abstracts Accession No. 106:95577 Romanenko et al., “Synthesis and Biological Activity of 3-Methyl, 7-or 8-alkyl-8-dialkyl, heterocyclic, and cyclohexylaminoxanthines,” Zaporozh. Med. Institute (1986).
Chemical Abstracts Accession No. 1987:95577: Abstract of Romanenko et al., “Synthesis and biological activity of 3-methyl, 7- or 8-alkyl, 7,8-dialkyl, heterocyclic, and cyclohexylaminoxanthines,” Zapoeozh, USSR, Farmatsevtichnii Zhurnal, 1986, (Kiev), vol. 5, 1986, pp. 41-44.
Chemical Abstracts Service, Database Accession number No. RN 668270-12-01, 2004, “1H-Purine-2,6-dione, 8-[(3R)-3-amino-1-piperidinyl]-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]”.
Chemistry Review: Tradjenta, “NDA 201280, CMC Director Review Tradjenta (Linagliptin) Tablets.” Center for Drug Evaluation and Research, Aug. 9, 2010, Retrieved from the internet on Nov. 1, 2013, http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201280Orig1s000ChemR.pdf.
Cheon, et al., Biochemical Pharmacology, “Inhibition of dipeptidyl IV by novel inhibitors with pyrazolidine scaffold”, 2005, vol. 70, p. 22-29.
Chiasson, J.-L. et al., “The Synergistic Effect of Miglitol Plus Metformin Combination Therapy in the Treatment of Type 2 Diabetes.” Diabetes Care, 2001, vol. 24, No. 6, pp. 989-994.
Chisari, A. et al. “Sulphinyl, Sulphonyl, and Sulphonium Groups as Leaving Groups in Aromatic Nucleophilic Substitutions.” Journal of the Chemical Society, Perkin Transactions II, 1982, pp. 957-959.
Chowhan, Z.T. et al., Drug-Excipient Interaction Resulting from Powder Mixing IV: Role of Lubricants and Their Effect on In Vitro Dissolution, Journal of Pharmaceutical Sciences, 1986, vol. 75, No. 6, pp. 542-545.
Clinical Trial NCT00622284 (published online at clinicaltrials.gov on Feb. 22, 2008).
Clinical Trial Protocol, “A Randomised, Double-blind, Placebo-controlled, Five Parallel Groups Study Investigating the Efficacy and Safety of BI 1356 BS.” Boehringer Ingelheim Pharmaceuticals, last updated on Jun. 24, 2014.
Clinical Trial, NCT00622284, clinicaltrials.gov, updated Feb. 22, 2008.
clinical Trials NCT00601250, clinicaltrials.gov, Jan. 25, 2008.
Clinical Trials, No. NCT00309608, “Efficacy and Safety of BI 1356 BS in Combination with Metformin in Patients With Type2 Diabetes” 2009, pp. 1-3.
Clinical Trials, No. NCT00622284, “Efficacy and Safety of BI 1356 in combination with metformin in patients with type 2 diabetes” 2012, pp. 1-5.
Clinical Trials. “View of NCT00601250 on Jan. 25, 2008: Efficacy and Safety of BI 1356 vs Placebo added to Metformin Background Therapy in Patients with Type 2 Diabetes” Clinical Trials. Gov Archive, [Online] Jan. 25, 2008 URL:http://clinicaltrials.gov/archive/NCTO0601250/2008_01_25 [retrieved on Feb. 27, 2009].
Clinical Trials. NCTO0622284. “Efficacy and safety of BI 1356 in combination with metformin in patients with type 2 diabetes” ClinicalTrials.gov (Online) No. NCT00622284, Feb. 13, 2008, p. 1-5, URL:http://clinicaltrial.gov/ct2/show/.
Clinical Trials. View of NCT00730275 updated on Aug. 7, 2008. “A study to assess the pharmacokinetics, safety and tolerability of Sitagliptin in adolescents”. http://clinicaltrials.gov/archive/NCT00730275/2008_08_07.
Clinical Trials: NCT00954447, View on Jun. 14, 2010. “Efficacy and Safety of Linagliptin in Combination with Insulin in Patients with Type 2 Diabetes”. <http://clinicaltrials.gov/archive/NCT00954447/2010_06_14>.
Clinical Trials: NCT00103857, “A Multicenter, Randomized, Double-Blind Factorial Study of the Co-Administration of MK0431 and Metformin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control” last updated on Apr. 27, 2015.
Clinical Trials: NCT00309608, “Efficacy and Safety of BI 1356 BS (Linagliptin) in Combination With Metformin in Patients With type2 Diabetes” Boehringer Ingelheim Pharmaceuticals, last updated on Jun. 24, 2014.
Clinical Trials: NCT00309608, “Efficacy and Safety of BI 1356 BS (Linagliptin) in Combination With Metformin in Patients With type2 Diabetes” Boehringer Ingelheim Pharmaceuticals, last updated: Dec. 11, 2013.
Clinical Trials: NCT00309608. Efficacy and safety of BI 1356 in combination with metformin in patients with type2 diabetes. Boehringer Ingelheim Pharmaceuticals, Jan. 27, 2009. Clinical Trials.gov . http://clinicaltrials.gov/archive/NCT00309608/2009_01_27.
Clinical Trials: NCT00602472. “BI 1356 in combination withe metformin and a sulphonylurea in Type 2 Diabetes”. DrugLib.com, Nov. 3, 2008. http://www.druglib.com/trial/08/NCT00309608.html.
Clinical Trials: NCT00622284. Efficacy and Safety of BI 1356 in Combination with Metformin in Patients with Type 2 Diabetes. Boehringer Ingelheim Pharmaceuticals, Aug. 2008. http://clinicaltrials.gov/archive/NCT00622284/2010_01_13.
Clinical Trials: NCT00798161. “Safety and efficacy of Bi 1356 Plus Metformin in Type 2 Diabetes, Factorial Design”. Clinical Trials.gov archive. A Service of the U.S> National Institutes of Health. Nov. 24, 2008, p. 1-3. http://clinicaltrials.gov/archive/NCT00798161/2008_11_24.
Colorcon, “Lactose Replacement with Starch 1500 in a Direct Compression Formula.” 2005, pp. 1-4.
Colorcon, “Reducing Coated Tablet Defects from Laboratory through Production Scale: Performance of Hypromellose or Polyvinyl Alcohol-Based Aqueous Film Coating Systems.” Opadry II, 2009, pp. 1-7.
Combs, D. W. et al., “Phosphoryl Chloride Induced Ring Contraction of 11,4-Benzodiazepinones to Chloromethylquinazolines”. J. Heterocyclic Chemistry, BD. 23, 1986, p. 1263-1264.
Conarello, S.L. et al., “Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance”. PNAS, May 27, 2003, vol. 100, No. 11, p. 6825-6830.
Conarello, S.L. et al; “Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance,” PNAS 2003; 100:6825-6830; originally published online May 14, 2003; information current as of Dec. 2006. www.pnas.org/cgi/content/full/100/11/6825.
Cotton, M.L. et al., “L-649,923—The selection of an appropriate salt form and preparation of a stable oral formulation.” International Journal of Pharmaceutics, 1994, vol. 109, Issue 3, pp. 237-249.
Craddy, P. et al., “Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison.” Diabetes Therapy, 2014, vol. 5, No. 1, pp. 1-41.
Crowe, E. et al., “Early identification and management of chronic kidney disease: summary of NICE guidance.” British Medical Journal, 2008, vol. 337, pp. 812-815.
“Betahistine diHCL CF 16 mg, tabletten,” Dutch Medicines Evaluation Board, Dated Apr. 13, 1988, Retrieved online from: <http://db.cbg-meb.nl/ords/f?p=111:3:0:SEARCH:NO::P0_DOMAIN,P0_LANG,P3_RVG1:H,EN,57626>.
“Betahistine diHCL CF 8 mg, tabletten,” Dutch Medicines Evaluation Board, Dated Apr. 13, 1988, Retrieved online from: <http://db.cbg-meb.nl/ords/f?p=111:3:0:SEARCH:NO::P0_DOMAIN,P0_LANG,P3_RVG1:H,EN,56227>.
“Sifrol 0,088 mg, tabletten,” Dutch Medicines Evaluation Board, Dated Oct. 14, 1997, Retrieved online from: <http://db.cbg-meb.nl/ords/f?p=111:3:0:SEARCH:NO::P0_DOMAIN,P0_LANG,P3_RVG1:H,EN,70120>.
“Sifrol 0,18 mg, tabletten,” Dutch Medicines Evaluation Board, Dated Oct. 14, 1997, Retrieved online from: <http://db.cbg-meb.nl/ords/f?p=111:3:0:SEARCH:NO::P0_DOMAIN,P0_LANG,P3_RVG1:11,EN,70121>.
“Sifrol 0,35 mg, tabletten,” Dutch Medicines Evaluation Board, Dated Nov. 16, 1999, Retrieved online from: <http://db.cbg-meb.nl/ords/f?p=111:3:0-SEARCH:NO::P0_DOMAIN,P0_LANG,P3_RVG1:H,EN,70673>.
“Sifrol 0,70 mg, tabletten,” Dutch Medicines Evaluation Board, Dated Oct. 14, 1997, Retrieved online from: <http://db.cbg-meb.nl/ords/f?p=111:3:0-SEARCH:NO::P0_DOMAIN,P0_LANG,P3_RVG1:H,EN,70122>.
“Sifrol 1,1 mg, tabletten,” Dutch Medicines Evaluation Board, Dated Oct. 14, 1997, Retrieved online from: <http://db.cbg-meb.nl/ords/f?p=111:3:0-SEARCH:NO::P0_DOMAIN,P0_LANG,P3_RVG1:H,EN,70124>.
Abstract for AU 2003280680, Jun. 18, 2004.
Abstract for AU 2009224546, Sep. 17, 2009.
Abstract in English for DE10109021, 2002.
Abstract in English for DE19705233, Aug. 13, 1998.
Abstract in English for DE2205815, 1972.
Abstract in English for EP0023032, 1981.
Abstract in English for JP 2002/348279, Dec. 4, 2002.
Abstract in English for JP 2003/286287, Oct. 10, 2003.
Abstract in English for KR20070111099, Nov. 11, 2007.
Actos Prescribing Information, 1999, pp. 1-26.
Adebowale, K.O. et al., “Modification and properties of African yam bean (Sphenostylis stenocarpa Hochst. Ex A. Rich.) Harms starch I: Heat moisture treatments and annealing.” Food Hydrocolloids, 2009, vol. 23, No. 7, pp. 1947-1957.
Ahren, B. et al., “Twelve- and 52-Week Efficacy of the Dipeptidyl Peptidase IV Inhibitor LAF237 in Metformin-Treated Patients With Type 2 Diabetes.” Diabetes Care, 2004, vol. 27, No. 12, pp. 2874-2880.
Ahren, Bo “Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin.” Vascular Health and Risk Management, 2008, vol. 4, No. 2, pp. 383-394.
Ahren, Bo, et al; Improved Meal-Related b-Cell Function and Insulin Sensitivity by the Dipeptidyl Peptidase-IV Inhibitor Vildagliptin in Metformin-Treated Patients with Type 2 Diabetes Over 1 Year; Diabetes Care (2005) vol. 28, No. 8 pp. 1936-1940.
Ahren, Bo; “DPP-4 inhibitors”, Best practice and research in clinical endocrinology and metabolism—New therapies for diabetes 200712 GB LNKD- DOI:10.1016/J. Beem.2007.07.005, vol. 21, No. 4, Dec. 2007, pp. 517-533.
Al-Masri, I.M. et al., “Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine.” Journal of Enzyme Inhibition and Medicinal Chemistry, 2009, vol. 24, No. 5, pp. 1061-1066.
Alter, M. et al., “DPP-4 Inhibition on Top of Angiotensin Receptor Bockade Offers a New Therapeutic Approach for Diabetic Nephropathy” Kidney and Blood Pressue Research, 2012, vol. 36, No. 1, pp. 119-130.
American Association of Clinical Endocrinologists, “Medical Guidelines for Clinical Practice for the Management of Diabetes Mellitus.” Endocrine Practice, 2007, col. 13, Suppl. 1, pp. 1-68.
American Diabetes Association, “Standards of Medical Care in Diabetes-2008.” Diabetes Care, Jan. 2008, vol. 31, Supplement 1, pp. S12-S54.
Anstee, Quentin M. et al. “Mouse models in non-alcholic fatty liver disease and steatohepatitis research” (2006) International Journal of Expermental Pathology, vol. 87, pp. 1-16.
Augeri, D.J. “Discovery and Preclinical Profile of Saxagliptin (GMB-477118): A Highly Potent, Long-Acting, Orally Active Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes”. Journal Med. Chem, 2005, vol. 48, No. 15, p. 5025-5037.
Augusti, D.V. et al., “Quantitative determination of the enantiomeric composition of thalidomide solutions by electrospray ionizatio tandem mass spectrometry”. Chem Comm, 2002, p. 2242-2243.
Augustyns, K. et al., The Unique Properties of Dipeptidyl-peptidase IV (DPP IV/CD 26) and the Therapeutic Potential of DPP-IV Inhibitors, Current Medicinal Chemistry, vol. 6, No. 4, 1999, pp. 311-327.
Aulinger, B.A. et al., “Ex-4 and the DPP-IV Inhibitor Vildagliptin have Additive Effects to Suppress Food Intake in Rodents”. Abstract No. 1545-P, 2008.
Aulton, Michael E., Pharmaceutics: The Science of Dosage Form Design, Second Edition, 2002, pp. 441-448.
Baetta, R. et al., “Pharmacology of Dipeptidyl Peptidase-4 Inhibitors.” Drugs, 2011, vol. 71, No. 11, pp. 1441-1467.
Balaban, Y.H.et al., “Dipeptidyl peptidase IV (DDP IV) in NASH patients” Annals of Hepatology, vol. 6, No. 4, Oct. 1, 2007, pp. 242-250, abstract.
Balbach, S. et al., “Pharmaceutical evaluation of early development candidates the 100 mg-approach.” International Journal of Pharmaceutics, 2004, vol. 275, pp. 1-12.
Balkan, B. et al, “Inhibition of dipeptidyl peptidase IV with NVP-DPP728 increases plasma GLP-1 (7-36 amide) concentrations and improves oral glucose tolerance in obses Zucker rates”. Diabetologia, 1999, 42, p. 1324-1331.
Banker, Gilbert S., “Prodrugs.” Modern Pharmaceutics Third Edition, Marcel Dekker, Inc., 1996, p. 596.
Bastin, R.J. et al., “Salt Selection and Optimization Procedures for Pharmaceutical New Chemical Entities”. Organic Process Research and Development, 2000, vol. 4, p. 427-435.
Beauglehole, Anthony R., “N3-Substituted Xanthines as Irreversible Adenosine Receptor Antagonists.” Ph.D. Thesis, Deakin University, Australia, 2000, pp. 1-168.
Beljean-Leymarie et al., Hydrazines et hydrazones hétérocycliques. IV. Synthèses de dérivés de I'hydrazine dans la série des imidazo[4,5-d]pyridazinones-4, Can. J. Chem., vol. 61, No. 11, 1983, pp. 2563-2566.
Berge, S. et al., “Pharmaceutical Salts.” Journal of Pharmaceutical Sciences, 1977, vol. 66, No. 1, pp. 1-19.
Bernstein, Joel “Polymorphism in Molecular Crystals.” Oxford University Press, 2002, p. 9.
Blech, S. et al., “The Metabolism and Disposition of the Oral Dipeptidyl Peptidase-4 Inhibitor, Linagliptin, in Humans”, Drug Metabolism and Disposition, 2010, vol. 38, No. 4, p. 667-678.
Bollag, R.J. et al; “Osteoblast-Derived Cells Express Functional Glucose-Dependent Insulinotropic Peptide Receptors,” Endocrinology, vol. 141, No. 3, 2000, pp. 1228-1235.
Borloo, M. et al. “Dipeptidyl Peptidase IV: Development, Design, Synthesis and Biological Evaluation of Inhibitors.” 1994, Universitaire Instelling Antwerpen, vol. 56, pp. 57-88.
Bosi, E. et al., “Effects of Vildagliptin on Glucose Control Over 24 Weeks in Patients With Type 2 Diabetes Inadequately Controlled With Metformin.” Diabetes Care, 2007, vol. 30, No. 4, pp. 890-895.
Boulton, D.W. et al., “Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Once-Daily Oral Doses of Saxagliptin for 2 Weeks in Type 2 Diabetic and Healthy Subjects.” Diabetes, 2007, Supplement 1, vol. 56, pp. A161.
Brazg, R. et al: “Effect of adding sitagliptin, a dipeptidyll peptidase-4 inhibitor, to metformin on 24-h glycaemic control and beta-cell function in patients with type 2 diabetes.” Diabetes, Obesity and Metabolism, Mar. 2007, vol. 9, No. 2, Mar. 2007 pp. 186-193.
Brazg, Ronald, et al; Effect of Adding MK-0431 to On-Going Metforming Therapy in Type 2 Diabetic Patients Who Have Inadequate Glycemic Control on Metformin; Diabetes ADA (2005) vol. 54, Suppl. 1 p. A3.
Brittain, H.G., “Methods for the Characterization of Polymorphs: X-Ray Powder Diffraction,” Polymorphism in Pharmaceutical Solids, 1999, p. 235-238.
March, J. “Advanced Organic Chemistry: Reactions, Mechanisms, and Structure”. Fourth Edition, 1992, pp. 652-653.
Mathieu, C. et al., “Antihyperglycaemic therapy in elderly patients with type 2 diabetes: potential tole of incretin mimetics and DPP-4 inhibitors.” International Journal of Clinical Practice, 2007, vol. 61, Suppl. 154, pp. 29-37.
Matsumiya, Teruhiko, et al., “Therapeutic Drugs for Clinicians” Diagnosis and Treatment (2008) vol. 96, No. 2 pp. 389-390.
Mayo Clinic Staff: “Nonalchoholic fatty liver disease: Prevention” [retrieved on Nov. 30, 2012]. retrieved from the Internet: ,URL: http://www.mayoclinic.com/health/nonalcoholic-fatty-liver-disease/DS00577DSECTION=prevention>.
McNay, David E.G. et al., “High fat diet causes rebound weight gain.” Molecular Metabolism, 2013, vol. 2, pp. 103-108.
Medline Plus, “Obesity” 2013, Retrieved from internet on Aug. 22, 2013, http://www.nlm.nih.gov/medlineplus/obesity.html.
Meece, J. “When Oral Agents Fail: Optimizing Insulin Therapy in the Older Adult”. Consultant Pharmacist, The Society, Arlington, VA US. vol. 24, No. Suppl B, Jun. 1, 2009, p. 11-17.
Mendes, F.D, et al. “Recent advances in the treatment of non-alcoholic fatty liver disease”. Expert Opinion on Investigational Drugs, vol. 14, No. 1, Jan. 1, 2005, p. 29-35.
Merck Manual of Diagnosis and Therapy: “Obesity.” 1999, 17th Edition, Chapter 5, pp. 58-62.
Merck: “Initial Therapy with Janumet (sitagliptin/metformin) provided significantly greater blood sugar lowering compared to metformin alone in patients with type 2 diabetes”. Webwire.com, Jun. 8, 2009, p. 1-4. http://www.webwire.com/ViewPressRel.asp?ald=96695.
Mikhail, Nasser, “Incretin mimetics and dipeptidyl peptidase 4 inhibitors in clinical trials for the treatment of type 2 diabetes.” Expert Opinion on Investigational Drugs, 2008, vol. 17, No. 6, pp. 845-853.
MIMS Jan. 2009, “Sitagliptin.” pp. 152-153.
Moritoh, Y. et al., “Combination treatment with alogliptin and voglibose increases active GLP-1 circulation, prevents the development of diabetes and preserves pancreatic beta-cells in prediabetic db/db mice.” Diabetes, Obesity and Metabolism, 2010, vol. 12, pp. 224-233.
Nabors, Lyn O'Brien “Alternative Sweeteners.” Marcel Dekker, Inc., 2001, pp. 235, 339-340.
Naik, R. et al., “Latent Autoimmune Diabetes in Adults.” The Journal of Clinical Endocrinology and Metabolism, 2009, vol. 94, No. 12, pp. 4635-4644.
Nar, Herbert “Analysis of Binding Kinetics and Thermodynamics of DPP-4 Inhibitors and their Relationship to Structure.” 2nd NovAliX Conference: Biophysics in drug discovery, Strasbourg, France, Jun. 9-12, 2015.
Nathan, D. et al., “Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy.” Diabetes Care, Aug. 2006, vol. 29, No. 8, pp. 1963-1972.
National Program for Care Guidelines, “Type 2 Diabetes mellitus.” 2002, First Edition, pp. 1-50.
Nauck, M. A. et al., “Efficacy and Safety of Adding the Dipeptidyl Peptidase-4 Inhibitor Alogliptin to Metformin Therapy in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A Multicentre, Randomised, Double-Blind, Placebo-Cotrolled Study.” Clinical Practice, 2008, vol. 63, No. 1, pp. 46-55.
Nauck, M. A. et al., “Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor, Sitagliptin, Compared with the Sulfonylurea, Glipizide, in Patients with Type 2 Diabetes Inaduately Controlled on Metformin alone: A Randomized, Double-Blind, Non-Inferiority Trial.” Diabetes Obesity and Metabolism, 2007, vol. 9, No. 2, pp. 194-205.
Nielsen, L., “Incretin Mimetics and DPP-IV Inhibitors for the Treatment of Type 2 Diabetes.” Drug Discovery Today, 2005, vol. 10, No. 10, pp. 703-710.
Nihon Ijinpo, Japan Medicinal Journal, 2001, No. 4032, p. 137.
Novartis AG, Investor Relations Release, “Galvus, a new oral treatment for type 2 diabetes, receives positive opinion recommending European Union approval.” Securities and Exchange Commission, Form 6-K, 2007, pp. 1-4.
O'Farrell, et al., “Pharmacokinetic and Pharmacodynamic Assessments of the Dipeptidyl Peptidase-4 Inhibitor PHX1149: Double-Blind, Placebo-controlled, Single-and Multiple-Dose Studies in Healthy Subjects”. Clinical Therapeutics, Excerpta Medica, Princeton, NJ, vol. 29, No. 8, 2007, p. 1692-1705.
Office Action for U.S. Appl. No. 10/695,597 dated May 2, 2008.
Oz, Helieh S., “Methionine Deficiency and Hepatic Injury in a Dietary Steatohepatitis Model.” Digestive Diseases and Sciences, 2008, vol. 53, No. 3, pp. 767-776.
Patani George A. et al.: “Bioisoterism : A Rational Approach in Drug Design”, Chemical Reviews, 1996, vol. 96, No. 8, pp. 3147-3176.
Pearson, E. R. et al., “Variation in TCF7L2 Influences Therapeutic Response to Sulfonylureas.” Diabetes, 2007, vol. 56, pp. 2178-2182.
Pei, Z.: “From the bench to the bedside: Dipeptidyl peptidase IV inhibitors, a new class of oral antihyperglycemic agents” Current Opinion in Drug Discovery and Development, Current Drugs, London, GB vol. 11, No. 4, Jul. 1, 2008 pp. 512-532.
Pietruck, F. et al., “Rosiglitazone is a safe and effective treatment option of new-onset diabetes mellitus after renal transplantation.” Transplant International, 2005, vol. 18, pp. 483-486.
Pilgaard, K. et al., “The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men.” Diabetologia, 2009, vol. 52, pp. 1298-1307.
Plummer, C.J.G. et al., “The Effect of Melting Point Distributions on DSC Melting Peaks.” Polymer Bulletin, 1996, vol. 36, pp. 355-360.
Pospisilik, et al; Dipeptidyl Peptidase IV Inhibitor Treatment Stimulates ?—Cell Survival and Islet Neogenesis in Streptozotocin-Induced Diabetic Rats; Diabetes, vol. 52, Mar. 2003 pp. 741-750.
Poudel, Resham R., “Latent autoimmune diabetes of adults: From oral hypoglycemic agents to early insulin.” Indian Journal of Endocrinology and Metabolism, 2012, vol. 16, Supplement 1, pp. S41-S46.
Pratley, R. et al., “Inhibition of DPP-4: a new therapeutic approach for the treatment of type 2 diabetes.” Current Medical Research and Opinion, 2007, vol. 23, No. 4, pp. 919-931.
Prescribing Information, Package insert for Leprinton tablets 100mg, Manufacturer: Tatsumi Kagaku Co., Ltd., Mar. 2003, pp. 1-3.
Priimenko, B. A., et al; Synthesis and Pharmacological Activity of Derivates of 6,8-Dimethyl Imidazo(1,2-f) Xanthine-(Russ.); Khimiko-Farmatsevticheskii zhurnal (1984) vol. 18, No. 12 pp. 1456-1461.
Radermecker, Regis et al., “Lipodystrophy Reactions to Insulin.” American Journal of Clinical Dermatology, 2007, vol. 8, pp. 21-28.
Rask-Madsen, C. et al., “Podocytes lose their footing.” Nature, 2010, vol. 468, pp. 42-44.
Rhee et al.: “Nitrogen-15-Labeled Deoxynucleosides. 3. Synthesis of [3-15N]-2′-Deoxyadenosine” J. Am. Chem. Soc. 1990, 112, 8174-8175.
Rosenbloom, et al., “Type 2 Diabetes mellitus in the child and adolescent”, Pediatric Diabetes, 2008, p. 512-526.
Rosenstock, et al., “Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component montherapy in patients with type 2 diabetes”. Diabetes, Obesity and Metabolism, Mar. 2007, vol. 9, No. 2, p. 175-185.
Rosenstock, et al., Sitagliptin Study 019 Groups, Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin, Clinical Therapeutics, 2006, vol. 28, Issue 10, p. 1556-1568.
Rosenstock, J. et al., “Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA1c without causing weight gain or increased hypoglycaemia”. Diabetes, Obesity and Metabolishm, Dec. 2009, vol. 11. No. 12, p. 1145-1152.
Rosenstock, J. et al., “Triple Therapy in Type 2 Diabetes.” Diabetes Care, 2006, vol. 29, No. 3, pp. 554-559.
Rowe, R. et al., Handbook of Pharmaceutical Excipients, Fifth Edition, Pharmaceutical Press, 2006, pp. 389-395, 449-453, and 731-733.
Rowe, R. et al., Handbook of Pharmaceutical Excipients, Fourth Edition, Pharmaceutical Press and American Pharmaceutical Association, 2003, pp. 323-332.
Russell-Jones, D. et al., “Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.” Diabetologia, 2009, vol. 52, pp. 2046-2055.
Salomon, J., et al; Ultraviolet and g-Ray-Induced Reactions of Nucleic Acid Constituents. Reactions of Purines with Amines; Photochemistry and Photobiology (1974) vol. 19 pp. 21-27.
Sarafidis, P. et al., “Cardiometabolic Syndrome and Chronic Kidney Disease: What is the link?” JCMS 2006, 1: p. 58-65.
Merck Index, 15th Ed., Linagliptin, 2013.
Janumet dosing instructions, Highlights of Prescribing information, 2008.
Ennis, Handbook of Pharmaceutical Granulation Technology, Theory of Granulation, 2010.
Houben-Weyl, Oxygen Compounds, Methods of Organic Chemistry, 1929.
Slotta, On Biguanides, Chem. Institute at the Univ. of Wroclaw, vol. 62, 1929.
Laugesen, Latent Autoimmune diabetes of the adult: current knowledge and uncertainty, vol. 10, 2015., Diabetic medicine.
Johansen, Diabetes Care, C-peptide Levels in latent Automimmune Diabetes in Adults treated with Linagliptin vs. Glimepiride, vol. 37, 2014.
Drucker, Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line, Proc. Natl. Acad. Sci, vol. 84, a97.
Mojsov, Insulintropin: Glucagin like peptide: Lab of Molecular Endocrinology, vol. 79, 1987, p. 616-619.
Holst,Role on incretin hormones in the regulation of insulin, Am j. Physiol Endocrinol Metab., 2004.
Matsuyama, Glucagen like peptide: a ptotent glucagonostatic hormone, Diabetes Research, 1988, p. 281-288.
Wettergren, Truncated GLP-1, Inhibits Pancreatic and Gastric Functions in Man, 1993, p. 665-673.
Li, Glucagen like Peptide 1 Receptor Signaling Modulates b cell apoptosis, Journal of Biological Chem, 2003.
Drug Data Report, 1994, Source, Smith Kline Beechman, Treatments for Septic Shock, p. 459.
Horie, Biomedcentral, Design, statistical analsysis and sample size calculation of a phase IIb/III study of linagliptin vs. voglibose and placebo, 2009.
International Search report for PCT/EP2019/069126, dated Oct. 2, 2019.
Press, Synthesis of 5,6 Dimethoxyquinazolin-2(1-H) ones, J. Heterocyclic Chwm, 1986.
Adams, Pub Pharmafile, 2011, Boehringer-lilly launch diabetes drug tradjenta in US.
Excerpt from Orange Book of Product Tradjenta, Feb. 5, 2011.
Roy, Pharmaceutical Impurities, PharmSciTech, 2002.
Publication Boehringer Ingelheim and Lilly's New type 2 Diabetes Treatment tradjenta, 2015, p. 1-7.
Donelly, Vascular Complications of Diabetes, MBJ, vol. 320, 2000.
Smithies, The Jackson Lab, Mouse Strain Datasheet, 2019, p. 1-2.
American Diabetes Assoc., Diagnosis and Classification of Diabetes Mellitus, vol. 29, 2006.
Deshpande, American Physical Therapy Assoc., Epidemiology of Diabetes related complications, 2008, vol. 88.
Vichayanrat, A. et al., “Efficacy and safety of voglibose in comparison with acarbose in type 2 diabetic patients.” Diabetes Research and Clinical Practice, 2002, vol. 55, pp. 99-103.
Vickers, 71st Scientific Session of the American Diabetes Association, “The DPP-4 inhibitor linagliptin is weight neutral in the DIO rat but inhibits the weight gain of DIO animals withdrawn from exenatide”, vol. 60, Jul. 2011.
Villhauer, E.B., “1-[[3-Hydroxy-1-adamantyl)amino]acetyl]-1-cyano-(S)-pyrrolidine: A Potent, Selective, and Orally Bioavailable Dipeptidyl Peptidase IV Inhibitor with Antihyperglycemic Properties” Journal Med. Chem, 2003, 46, p. 2774-2789.
Villhauer, E.B., et al., “1-{2-{5-Cyanopyridin-2-yl)amino}-ethylamino}acetyl-1-1(S)-pyrrolidine-carbonitrile: A Potent, Selective, and Orally Bioavailable Dipeptidyl Peptidase IV Inhibitor with Antihyperglycemic Properties”. Journal of Medical Chemistry, 2002, vol. 45, No. 12, p. 2362-2365.
Vincent, S.H. et al., “Metabolism and Excretion of the Dipeptidyl Peptidase 4 Inhibitor [14C]Sitagliptin in Humans.” Drug Metabolism and Disposition, 2007, vol. 35, No. 4, pp. 533-538.
Wang, Y. et al., “BI-1356. Dipeptidyl-Peptidase IV Inhibitor, Antidiabetic Agent.” Drugs of the Future, 2008, vol. 33, No. 6, pp. 473-477.
Weber, Ann E., “Dipeptidyl Peptidase IV Inhibitors for the Treatment of Diabetes.” Journal of Medicinal Chemistry, 2004, vol. 47, pp. 4135-4141.
WebMD, Autoimmune Diseases: What Are They? Who Gets Them? “What Are Autoimmune Disorders?” 2015, pp. 1-3. Retrieved online Jul. 9, 2015. http://www.webmd.com/a-to-z-guides/autoimmune-diseases.
Wertheimer, et al., “Drug Delivery Systems improve pharmaceutical profile and faciliate medication adherence”, Adv. Therapy 22: p. 559-577 (2005).
White, John R. Jr., “Dipeptidyl Peptidase-IV Inhibitors: Phamacological Profile and Clinical Use”. Clinical Diabetes, Apr. 2008, vol. 26, No. 2, pp. 53-57.
Wikipedia, “Linagliptin” Sep. 12, 2015. <https://en.wikipedia.org/w/index.php?title=Linagliptin&oldid=333469979>.
Wikipedia, Annulation. Jun. 23, 2008, http://en.wikipedia.org/wiki/Annelation.
Williams-Herman, D. et al., “Efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes: a 54-week study”. Current Medical Research and Opinion, Informa Healthcare, GB, vol. 25, No. 3, Jan. 2009, p. 569-583.
Wirth, D. et al., “Maillard Reaction of Lactose and Fluoxetine Hydrochloride, a Secondary Amine.” Journal of Pharmaceutical Sciences, 1998, vol. 87, No. 1, pp. 31-39.
Witteles, R. M. et al., “Dipeptidyl Peptidase 4 Inhibition Increases Myocardial Glucose Uptake in Nonischemic Cardiomyopathy.” Journal of Cardiac Failure, 2012, vol. 18, No. 10, pp. 804-809.
Wolff, M.E.: “Burger's Medicinal Chemistry and Drug Discovery” Fifth Edition, vol. 1: Principles and Practice, pp. 975-977, 1994, John Wiley & Sons, Inc.
World Health Organization (WHO). “Addendum 1 to “The use of stems in the selection of International Nonproprietary names (INN) for pharmaceutical substances”” Online Jun. 19, 2007, pp. 1-3, retrieved from URL: http://www.who.int/medicindedocs/index/assoc/s1414e/s1414e.pdf.
X-Ray Diffraction. The United States Pharmacopeia, 2002, USP 25 NF20, p. 2088-2089.
Yale, Jean-Francois, “Oral Antihyperglycemic Agents and Renal Disease: New Agents, New Concepts.” Journal of the American Society of Nephrology, 2005, vol. 16, Suppl. 1, pp. S7-S10.
Yamagishi, S. et al., “Pleiotropic Effects of Glucagon-like Peptide-1 (GLP-1)-Based Therapies on Vascular Complications in Diabetes.” Current Pharmaceutical Design, 2012, vol. 17, pp. 4379-4385.
Yap, W.S. et al., “Review of management of type 2 diabetes mellitus.” Journal of Clinical Pharmacy and Therapeutics, 1998, vol. 23, pp. 457-465.
Yasuda, et al. “E3024 3-but-2-yny1-5-methyl-2-piperazin-1-y1-3,5-dihydro-4H-imidazol [ 4,5-d]pyridazin-4-one tosylate, is a move, selective and competitive dipeptidyl peptidase-IV inhibitor”. European Journal of Pharmacology, vol. 548, No. 1-3, Oct. 24, 2006, p. 181-187. Abstract.
Yasuda, N. et al., “Metformin Causes Reduction of Food Intake and Body Weight Gain and Improvement of Glucose Intolerance in Combination with Dipeptidyl Peptidase IV Inhibitor in Zucker fa/fa Rats.” The Journal of Pharmacology and Experimental Therapeutics, 2004, vol. 310, No. 2, pp. 614-619.
Yokoyama< “Prevalence of albumineria and renal insufficiency and associated clinical factors in type 2 diabetes: the Japan Diabetes clinical data Management study(JDDM15)” Nephrol Dial Transplant (2009) 24: 1212-1219 Advance Access Pub 2008.
Yoshikawa, Seiji et al.: Chemical Abstract of Japanese Patent No. WO 2003/104229 Preparation of purinone derivatives as dipeptidylpeptidase IV (DPP-IV) inhibitors, 2003.
Yoshioka, S. et al., “Stability of Drugs and Dosage Forms.” Kluwer Academic Publishers, 2002, pp. 30-33.
Youssef, S. et al., “Purines XIV. Reactivity of 8-Promo-3,9-dimethylxanthine Towards Some Nucleophilic Reagents.” Journal of Heterocyclic Chemistry, 1998, vol. 35, pp. 949-954.
Zander, M. et al., “Additive Glucose-Lowering Effects of Glucagon-Like Peptide-1 and Metformin in Type 2 Diabetes.” Diabetes Care, 2001, vol. 24, No. 4, pp. 720-725.
Zeeuw, D. et al., “Albuminuria, a Therapeutic Target for Cardiovascular Protection in Type 2 Diabetic Patients With Nephropathy.” Circulation, 2004, vol. 110, No. 8, pp. 921-927.
Zejc, Alfred, et al; “Badania Nad Piperazynowymi Pochodnymi Dwumetyloksantyn” Acta Polon Pharm, XXXV (1976) Nr. 4 pp. 417-421.
Zerilli, T. et al., “Sitagliptin Phosphate: A DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus.” Clinical Therapeutics, 2007, vol. 29, No. 12, pp. 2614-2634.
Zhimei, Xiao et al., “Study progression of oral drugs for treatment of type II diabetes.” Drug Evaluation, 2004, vol. 1, No. 2, pp. 138-143.
Zhong, Qing et al; “Glucose-dependent insulinotropic peptide stimulates proliferation and TGF-? release from MG-63 cells,” Peptides 24 (2003) 611-616.
Zhu, G. et al., “Stabilization of Proteins Encapsulated in Cylindrical Poly(lactide-co-glycolide) Implants: Mechanism of Stabilization by Basic Additives.” Pharmaceutical Research, 2000, vol. 17, No. 3, pp. 351-357.
Zimdahl, H. et al., “Influence of TCF7L2 gene variants on the therapeutic response to the dipeptidylpeptidase-4 Inhibitor linagliptin.” Diabetologia, 2014, vol. 57, pp. 1869-1875.
Zimmer et al; Synthesis of 8-Substituted Xanthines and their Oxidative Skeleton Rearrangement to 1-Oxo-2,4,7,9-tetraazaspiro[4,5]dec-2-ene-6,8,10-triones; Euripean Journal Organic Chemistry (1999) vol. 9 pp. 2419-2428.
Jibiinkoka-Tenbo, Vision of Otorhinolaryngology, How to use anti-microbial drug in a patient with impairment of renal function, vol. 44, No. 3, 2001, p. 217-220.
Rinsho-Yakuri, Jpn. J. Clin. Pharmacol. Ther. Pharmacokinetics: excretion, 30(3) 1999.
Fiorucci, et al. Trends in Molecular Medicine, Targeting farnesoid X receptor for liver and metabolic disorders, 13(7), 2007, p. 298-309.
Morhenn, “Keratinacyte proliferation n wound healing and skin diseases”, Immunology Today, vol. 9, Issue 4, 1988, p. 104.
Boehringer Ingelheim Pharmceuticals, Inc. v. HEC Pharm Co., Ltd., et al., No. 15-cv-5982, United States District Court for the District of New Jersey, Dec. 8, 2016.
Karaliede et al, Diabetes Care, Endothelial Factors and Diabetic Nephropathy, 2011, 34, Suppl 2, p. 291-296.
Hansen, European Journal of Pharmacology, “The DPP-IV inhibitor linagliptin and GLP-1 induce synergistic effects on body weight loss and appetite suppression in the diet-induced obese rat”, 2014, p. 254-263.
Ferreira, Triple Combination therapy with sitagliptin, metformin and rosiglitazone improves glycaemic control in patiens with type 2 diabetes, Diabetologixa, 2008, Suppl 1.
Byrn, Pharmaceutical Solids, a Strategic Approach to Regulatory Considerations, Pharmaceutical Research, 1995, vol. 12.
Morhenn (2), Keratinocyte proliferation in wound healing and skin diseases, Immunology Today, vol. 9, 1994.
Diabetes, Type 1 Diabetes-Associated Autoantibodies, 2009, vol. 52, Issue 8, p. 675-677.
Merck manual, 18th Edition, published Apr. 25, 2007, p. 594-598, Japanese Edition.
Scientific Discussion on Sifrol, EMEA, 2005, p. 1-9.
Scientific Discussion for Sifrol, European Public Assessment Reports, 2005, p. 1.
Hu, Y. et al., “Synthesis and Structure-activity Relationship of N-alkyl Gly-boro-Pro Inhibitors of DPP4, FAP, and DPP7.” Bioorganic & Medicinal Chemistry Letters 15, 2005, pp. 4239-4242.
Huettner Silks et al: “BI 1356, a novel and selective xanthine based DPP-IV inhibitor, demonstrates good safety and tolerability with a wide therapeutic window” Diabetes< American Diabetes Association, US, vol. 56, No. Suppl 1, Jun. 1, 2007, p. A156.
Hull, R. et al., “Nephrotic syndrome in adults.” British Medical Journal, 2008, vol. 336, pp. 1185-1190.
Hunziker, D. et al, “Inhibitors of DPP IV-recent advances and structural views”, Current Topics in Medicinal Chemistry, 2005, vol. 5 issue 16, pp. 1623-1637.
Huttner, S. et al., “Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of BI 1356, an Inhibitor of Dipeptidyl Peptidase 4, in Healthy Male Volunteers.” Journal of Clinical Pharmacology, 2008, vol. 48, No. 10, pp. 1171-1178.
International Search Report—European Search Report for PCT/EP2003/09127 dated Mar. 1, 2011.
International Search Report and Written Opinion for PCT/EP2006/064657 dated Nov. 2, 2006.
International Search Report and Written Opinion for PCT/EP2007/054201 dated Aug. 29, 2007.
International Search Report and Written Opinion for PCT/EP2007/054270 dated Aug. 14, 2007.
International Search Report and Written Opinion for PCT/EP2008/060740 dated Mar. 30, 2009.
International Search Report and Written Opinion for PCT/EP2009/053978 dated Sep. 29, 2009.
International Search Report and Written Opinion for PCT/EP2009/056722 dated Aug. 13, 2009.
International Search Report and Written Opinion for PCT/EP2009/060521 dated Mar. 9, 2010.
International Search Report and Written Opinion for PCT/EP2009/063511 dated Feb. 26, 2010.
International Search Report and Written Opinion for PCT/EP2009/067772 dated Apr. 14, 2010.
International Search Report and Written Opinion for PCT/EP2010/050103 dated Mar. 22, 2010.
International Search Report and Written Opinion for PCT/EP2010/051093 dated Jul. 14, 2010.
International Search Report and Written Opinion for PCT/EP2010/051817 dated Jun. 8, 2010.
International Search Report and Written Opinion for PCT/EP2010/064691 dated Apr. 6, 2011.
International Search Report and Written Opinion for PCT/EP2010068349 dated Feb. 4, 2011.
International Search Report and Written Opinion for PCT/EP2011/054169 dated Aug. 4, 2011.
International Search Report and Written Opinion for PCT/EP2011/057163 dated Jun. 27, 2011.
International Search Report and Written Opinion for PCT/EP2011/057256 dated Jul. 22, 2011.
International Search Report and Written Opinion for PCT/EP2011/060449 dated Sep. 27, 2011.
International Search Report and Written Opinion for PCT/EP2011/070156 dated Jan. 17, 2012.
International Search Report and Written Opinion for PCT/EP2012/053910 dated May 14, 2012.
International Search Report and Written Opinion for PCT/EP2012/063852 dated Sep. 6, 2012.
International Search Report and Written Opinion for PCT/EP2012/077024 dated Feb. 19, 2013.
International Search Report and Written Opinion for PCT/EP2013/054524 dated Apr. 24, 2013.
International Search Report and Written Opinion for PCT/EP2013/059828 dated Aug. 6, 2013.
International Search Report and Written Opinion for PCT/EP2013/059831 dated Aug. 9, 2013.
International Search Report and Written Opinion for PCT/EP2013/060311 dated Aug. 9, 2013.
International Search Report and Written Opinion for PCT/EP2013/060312 dated Sep. 4, 2013.
International Search Report and Written Opinion for PCT/EP2013/070978 dated Oct. 31, 2013.
International Search Report and Written Opinion for PCT/EP2014/055113 dated May 16, 2014.
International Search Report and Written Opinion for PCT/EP2014/062398 dated Aug. 20, 2014.
International Search Report and Written Opinion for PCT/EP2015/054114 dated May 12, 2015.
International Search Report and Written Opinion for PCT/EP2015/074030 dated Feb. 4, 2016.
International Search Report and Written Opinon for PCT/EP2007/054204 dated Aug. 3, 2007.
International Search Report for PCT/EP03/12821 dated Mar. 30, 2004.
International Search Report for PCT/EP03/13648 dated Apr. 5, 2004.
International Search Report for PCT/EP2002/01820 dated May 7, 2002.
International Search Report for PCT/EP2003/12821 dated Mar. 30, 2004.
International Search Report for PCT/EP2003/13648 dated Apr. 5, 2004.
International Search Report for PCT/EP2005/001427 dated May 23, 2005.
International Search Report for PCT/EP2005/055711 dated Mar. 29, 2006.
International Search Report for PCT/EP2007/054204 dated Mar. 8, 2007.
International Search Report for PCT/EP2007/058181 dated Nov. 28, 2007.
International Search Report for PCT/EP2008/060738 dated Nov. 5, 2008.
International Search Report for PCT/EP2009/060170 dated Oct. 28, 2009.
The Textbook of Pharmaceutics, Pharmcaeutical Subcommitee Hanrimwon, 2005, p. 1-6.
Mettler Toledo “interpreting DSC curves Part 1: Dynamic Measurements” Jan. 2000. Available from www.masointechnology.ie.x/Usercom_11.pdf.
Glucophage (metformin hydrocholoride tablets) revised label, 2003.
Stahl, Selected Procedures for the Preparation of Pharmaceutically Acceptable salts, Handbook of Pharmaceutical Salts Properties, Chapter 11, 2015.
Caira, Crystalline Polymorphism of Organic Compounds, Topics in Current Chemistry, vol. 198, 2015.
Brittain, Polymorphism on Pharmaceutical Solids, Chapter 5 Generation of Polymorphs, vol. 95, 1999, p. 183-226.
Luo, Theory and Practice of Modern Physical Pharmacy, Shangai Scientific and Technical Literature Publishing House, 2005, p. 294.
Thomas, (R)-8-Amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione(BI1236, a Novel Xanthine based Dipeptidyl Peptidase 4 inhibitor, has a Superior Potency and longer duration of action compared with other dipeptyl Peptidase-4 inhibitors, The Journal of Pharmacology and Experimental Therapeutica, vol. 325, 2008, p. 175-182.
Kim, Comparison of DPP-4 Inhibitors, The Journal of Korean Diabetes, http:dx.doi.org/10.4093/jkd.2013.14.3.111.
Medicine Department of Pharmacy, Pharmaceutical Subcommitte, Book Publishing Harwinton, 1996, p. 283.
Huang, et al. Elimination of metformin-croscarmellose sodium interaction by competition, International Journal of Pharmaceutics, 2006, p. 33-39.
Freeman, Initial Combination therapy for patients with type 2 diabetes mellitus, Drugs in Context, 2013, p. 212256.
Scheen, Efficacy and Safety of Jentadueto, Expert Opinion on Drug and Safety, vol. 12, No. 2, 2013, p. 275-289.
Haak, Initial Combination of linagliptin and metformin improves glycemic control in type 2 diabetes, Diabetes, Obesity and Metabolism, vol. 14, 2012, p. 565-574.
International Search Report and Written Opinion for PCT/EP2017/064007, dated Jun. 8, 2017.
Wikipedia, the free encyclopedia, The carbonyl group, 2017.
Controlling Temperature (Guidelines for the Storage of Essential Medicines and Other Health Commodities, 2003, http://apps.who.int.medicinedocs/en/d/Js4885e/6.5html).
Pharmaceutical Manufacturing and Storage (Concepts and Design, Inc.) 2009.
Methocel Cellulose Ethers in Aqueous Systems for tablet coating: retrieved from Internet: http;//msdssearch.dow.com/PublishedLiteratureDOWCOM/dh_004a/0901b8038004ab56.pdf?filepath=198-00755.pd?fromPage=GetDoc, published2002. Retrieved Dec. 8, 2017.
Wu, Reactive Impurities in Excipients-Profiling, American Association of Pharmaceutical Scientists, 2011, vol. 12, No. 4, p. 1248-1263.
Waterman, Accelerating aging-Prediction of Chemical Stability of Pharmaceuticals, International Journal of Pharmaceutics, 2005, vol. 293, p. 101-125.
Herman, The DP-IV inhibitor MK-0431 enhances active GLP-1 and reduces Glucose following an OGTT in Type 2 Diabetics, American Diabetes Asociation, 2004.
Kaur, Development of new incretin drugs: Promising Therapies, Indian Journal Pharmacology, 2006, vol. 38, Issue 2, p. 100-106.
Clinical Trial results of Tradjenta Tablet, Center for Drug Evaluation and Research, 2010.
Pregelatinized Starch, Drugs.com, derived from https://drugs.com/inactive/pregelatinized-starch-136.html, accessed Nov. 17, 2017.
The textbooks of Pharmaceutics, Department of Pharmacy, Pharmaceutical Committee, 1996.
The Textbooks of Pharmaceutics, Department of Pharmacy, Pharmaceutical Subcommitee, 2000.
Approval material for Tradjenta tablet, Trial 1218.2, Center for Drug Eval. and Research, 2011.
Development Guideline for Excellent Drug, 2008, MFDS.
Doopedia, Maillard Reaction.
Hu, Diabetes Mellitus and Cardiovascular Disease, People's Military Medical Press, 2005, p. 211.
Susman,ADA: Linagliptin Works in Diabetic Kidney Disease, Med Page Today, 2011.
Announcement of the approval of Novel oral Diabetes Drug JANUVIA, Press Release, 2006.
Okano, Renal Clearance, New General Pharmaceutics, Revised 3rd Edition, 1987p. 213-215.
Clinical trials, a Randomized, Double Blind, Active Controlled parallel Group Efficacy and Safety Study of BI 1356 Compared to Glimepiride over 2 years in Type 2 Diabetic Patients with insufficient glycemic control despite metformin therapy, https://clinicaltrials.gov/archive/NCT00622284/20120606, 2008.
Eckhardt, “-(3-(R)-Aminopiperidin-1 -yl)7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl-3,7-dihyd ropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes”, J. med. Chem, vol. 50, 2007.
Shigai, “How to use medicines in case of kidney injury caused by medicine” Journal of the Japanese Association of Rural Medicine, vol. 51, 2002, p. 63-67.
Zeng, “Efficacy and Safety of linagliptin added to metformin and sulphonylurea in Chinese patients with type 2 diabetes: a sub-analysis of data from a randomised clinicial trial”, Current Medical Research and Opinion, 2013.
Seino, Alogliptin plus voglibose in Japanese patients witrh type 2 diabetes: a randomized, double blind, placebo-controlled trial with an open label, long term extension, Current Medical Research and Opinion, 2011, vol. 27, p. 21-29.
Kurozumi, Efficacy of a-glucosidase inhibitors combined with dipeptyl-peptidase-4 inhibitor for glucose fluctuation in patients with type 2 diabetes mellitus by continuous glucose monitoring, Journal of Diabetes Investigation, 2013, vol. 4, p. 393-398.
Horikawa, Synergistic Efffect of a-glucosidase inhibitors and dipeptidyl peptidase 4 inhibitor treatment, Journal of Diabetes Investigation, 2011, vol. 2, p. 200-203.
Yamazaki, Comparison of Efficacies of a Dipeptidyl Peptidase IV Inhibitor and a-Glucosodase Inhibitors in Oral Carbohydrate and Meal Tolerance Tests and their Effects of their tolerance in mice, J. Pharmacol Science, 2007, p. 29-38.
Kawamori, Linagliptin monotherapy provides superior glycaemic control v. placebo or voglibose with comparable safety in Japanese patients with type 2 diabetes, a randomized , placebo and active comparator-controlled doiuble blind study, 2011, Diabetes, Obesity and Metabolism, p. 348-357.
Inagaki, Linagliptin provides effective, well-tolerated add-on therapy to pre-existing oral antidiabetic therapy over 1 year in Japanese patients with type 2 diabetes, Diabetes, Obesity and Metabolis, 2013, p. 833-843.
Tang, Protection of DPP-4 inhibitors on cardiovascular, Drug Evaluation, vol. 9, 2012, p. 6-9.
Han, Basic and Clinical Coronary Heart Disease, Jilin Univ. Press, 2012, p. 114-118.
Lakey, Technical Aspects of Islet Preparation, Translp, Int.m 2003, vol. 16, p. 613-632.
White, Cardiovascular Events in patients receiving alogliptin, Diabetes Pro, 2010, vol. 59, p. 391.
Johansen, Cardiovascular safety with linagliptin on patients with type 2 diabetes mellitus, Cardiovascular Diabetology, 2012, vol. 11, p. 1-10.
Pham, New Onset Diabetes Mellitus After Solid Organ Transplantation, Endocrinology and Metabolism Clinics of North America, 2007, p. 873-890.
Ahren, Vascular Health and Risk Management, Novel combination treatment of type 2 diabetes DPP-4 inhibition plus metformin, 2008, p. 383-394.
Fuchs, Journal of Pharmacy and Pharmacology, Concentration-dependent plasma protein binding of the novel dipeptidyl peptidase 4 inhibitor BI 1356 due to saturable binding to its target in plasma of mice, rats and humans, 2009.
Linagliptin, Pub Chem, Clinical Trial Search of Japan, https;//pubchem.ncbi.nlm.nih.gov/compound/10096344 dated Jun. 25, 2020.
Ristic, Diabetes, Obesity and Metabolism, Improved Glycemic Control with dipeptidyl peptidase-4 inhibition in patients in patients with type 2 diabetes, 2005.
Aschner, Emerging Treatments and Technologies, Effect of the Dipepttidyl Peptidase-4 Inhibitor Sitagliptin as Monotherapy on Glycemic Control in Patients with Type 2 Diabetes, vol. 29, 2006.
Levien, Diabetes Spectrum, New Drugs in Development for the Treatment of Diabetes, vol. 22, 2009.
Mikhail, Incretin mimetics and dipeptidyl peptidase 4 inhibitors in clinical trials, expert Opinion on Investigational Drigs, 2008.
Huettner, Diabetes, Novel and Selective Xanthine, Jun. 2007 Supplement vol. 56.
Heizmann, Xanthines as scaffold for molecular diversity, Molecular doversity, vol. 2, 1996, p. 171-174.
Rabinovitch, Theophylline protects against diabetes in BB rats, Diabetologica, 1990.
De galan, Theophylline Improves Hypoglycemia Unawareness, Diabetes, vol. 51, 2002.
Mark, A novel and Selective Xanthine Based Competitive DPP-IV Inhibitor, Diabetes, vol. 56, 2007.
Abdoh, Amlodipine Besylate-Excipients Interaction in Solid Dosage Form, Phamra Dev. and Strategy, 2018.
Bruni, Drug Excipient Compatibility Studiesm J. of Thermal Analysis, 2018.
Crowley, Drug-Excipient interactions, Pharma Tech Europe, vol. 13, 2001.
Macdonald, No fraud, no conspiracy, no error, Pharmatechnologist, 2017.
Hanrinwon, Pharmaceutical Subcommittee, Pharmaceutics, p. 284-288, 1995.
Nathan, Managment of Hyperglycemia in Type 2 Diabetes, Diabetes Care, vol. 31, 2008.
Eckhardt, 8-)3-(R)-Aminopiperidin-l-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3.7-dihyfropurine-2.6-dione (BI 1356), a highly potent, Selective, long-acting and Orally Bioavailable DPP-4 Inhibitor, J. Med Chem. vol. 50, 2007.
Forst, The novel, potent, and selective DPP-4 inhibitor, ADA Poster, 2007.
Heise, Pharmacokinetics, pharmacodynamics, and tolerablity of mutiple does of linagliptin, Diabetes, Obesity and Metabolism, vol. 11, 2009.
Schafer, Impaired glucagen like peptide 1 induced insulin secretions in carriers of transcription, Diabetologica, vol. 50, 2007.
Hu, Research and Application, Biomedical Info in Translational Research, 2008.
Pearson, Variation in TCF7L2Influences Therapeutic Response to Sulfonylreas, Diabetes, vol. 56, 2007.
Florez, Genetic Susteptibility to Type 2 Diabetes, J. of Diabetes, vol. 3, 2009.
Levien, New Drugs in Development for the Treatment of Diabetes, Diabetes Spectrum, vol. 22, 2009.
Graefe-Mody, Evaluation of the Potential for steady state phamracokinetic and pharmacodynamic interactions between the DPP-4 inhibitor linagliptin and metformin, Current Medical Research and Opinion, vol. 25, 2009.
Encyclopedia of Pharma Technology, Swarbrick, 3rd Ed., vol. 1, Absorption of Solid Surfaces, 2007.
Ahren, Emerging Dipeptyl peptidase-4 inhibitors for the treatment of diabetes, Expert Opinion on Emerging Drugs, vol. 13, 2008.
Ohlden, New data from Boehringer INgelheim's Ongoing Linagliptin Trial Programme Shows Promising Safety and Efficacy results, Newswire, 2020.
Lovshin, Incretin based therapies for type 2 diabetes mellitus, Nature, vol. 5, 2009.
Clinical Trials, NCT006002472, BI 1356 in combination with Metformin submitted Feb. 27, 2014.
Boehringer Ingelheim Press Release: Boehringer Ingelheim's diabetes Pipeline continues to advance as the company announces conclusion of robust Phase III pivotal trials programme for linalgiptin, Small Molecules, Published Sep. 28, 2009.
Wu, Primacy of the 3b Approach to Control risk factors for Cardiovascular dissease in type 2 diabetes patient,s Diabetes Mellitus and Cardio Disease, People's Military Press, 2005.
Diabetes and Foot Ulcers, www.diabetes.co.uk/diabetes-comolications/diabetic-foot-ulcers.html, 2018.
Nationale Versorgungs-Leitlinie, Diabetes Mellitus, 2004.
Deutsche Evidenzbasierte Diabetes-Leitlinien, Diabetes and Herz, 2002.
Menielly, Diabetes in Elderly adults, J. of Gerontolgy, vol. 56A, 2001.
Herrington, Metformin, Effective ans safe in renal Disease? Int. Urol. Nephrol. vol. 40, 2008.
Bruni, Drug Excipient compatibility, Journal of Thermal Analysis and Calorimetry, vol. 68, 2002.
Kibbe, Handbook of Pharmaceutical Excipients, 3rd Edition, 2009, p. 104-107.
Abdoh, Amlodipine besylate excipients interaction in solid dosage form, Pharmaceutical Development and Technology, vol. 9, 2004.
Crowley, Drug-Excipients Interactions, Pharmaceutical Technology Europe, vol. 13, 2001.
Wade, Organic Chem, 6th Edition, 2006, p. 918, 943-956.
News Article, https:/www.in-phamratechnologist.com-Article-France-and-maerck-say-reformulated-Euthyrox-is-safe.)—Sep. 17, 2017.
Hu, Diabetes Mellitus and Heart Disease, People's Military Press, 2005.
Nursten, The Mailard Reaction, Chemistry, Biochemistry, and Implications, Chapter 10, p. 1-8., 2018.
DiFeo, Drug Product Development, A Technical Review of Chemistry, Drug Development and Industrial Pharmacy, vol. 29, 2003, p. 939-958.
Federal register, Department of Health and Human Services, vol. 62, 1997.
Van Veen, Compaction of Powder blends, University Medical Center, 2003.
MacDonald, No Fraud, no conspiracy, no error, France and Merck say reformulated Euthyrox is safe, Pharmatechnolgist, 2017.
Nachaegari, Coprocessed Excipients for Solid Dosage Forms, Pharmaceutical technology, 2004.
Gohel, A review of coprocessed Directly compressible excipients, J. Pharm Pharmaceutical Sci, 2005.
Cotton, The Selection of an appropriate salt form and preparation of a stable oral formulation, International Journal of Pharmaceutics, 1994, p. 237-249.
Ahmed, Materials Formulation of Low Dose Medicines, Americal Pharma review, vol. 3, 2000.
Wikipedia, Polyvinylpyrrolidone, https:en.wikipedia.org/wiki/access date May 15, 2018.
Westerhuis, Optimisation of the composition and production of mannitol cellulose tablets International Journal of Pharmaceutics, 1996, p. 143, 151-162.
Portincasa, Current Pharmacological Treatment of Nonalcoholic Fatty Liver, Current Medicinal Chem, 2006, p. 2889-2900.
Del Prato, Diabetes, Obesity and Metabolism, Effect of linagliptin monotherapy on glycemic control and markers of b-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial, 2011, p. 258-267.
Gallwitz, linagliptin—A novel Dipeptidyl Peptidase Inhibitor for Type 2 Diabetes Therapy, Clinical Medicine Indights: Endocrinology and Diabetes, 2012, vol. 5, p. 1-11.
Lakey, Technical Aspects of islet preparation and transplantation, Burridge Medical Researach Institute, 2003.
Mikhail, Investigating Drugs, Incretin Mimetics and dipeptidyl peptidase 4 inhibitors in clinical trials for the treatment of Type 2 diabetes, vol. 17, 2008, p. 845-853.
Cefalu, Animal Models of Type 2 Diabetes: Clinical Presentation and Pathophysiological Relevance to the Human Condition, ILAR Journal, vol. 47, No. 3, 2006.
Crowe, Early Guidelines and Identification Management of Chronic Kidney Disease, 2008, summary of NICE guidance, vol. 337, p. 812-815.
Zaman, Comparison Between Effect of Vildagliptin and Linagliptin on Glycaemic control, renal function, liver funstion and lipid profile in patients of T2DM Inadequately controlled with combo of Metformin and Glimepiride, Journal of Dental and Medical Sciences, vol. 16, Issue 9, 2017. p. 27-31.
Connelly, Dipeptyl peptidase-4 inhibition improves left ventricular function in chronic kidney disease, Clinical and Investigative Medicine, vol. 37, p. 172-185, 2014.
Scheen, Clinical Pharmacokinetics of metformin, Clinical Pharmacokinetics, vol. 30, No. 5, 1996, p. 359-371.
Zhang, Classification and Treatment Prinicples of Diabetes, Beijing Medical Univ and China Union Medical Univ. Joint Publishing House. 1st ed., 1998, p. 389.
Diabetes and Foot ulcers, www.diabetes.co.uk/diabetes-complications/diabetic-foot-ulcers.html, 2018.
Aronow, Congestive Heart Failure, Treatment of Heart Failure in Older Persons with Coexisting Conditions, vol. 9, No. 3, 2003, p. 142-147.
Tiwari, Linagliptin, A dipeptyl peptidase-4 inhibitor for the treatment of type 2 diabetes, Current Opinion in Ivestigational Drugs, vol. 10, 2009, p. 1091-1104.
Isomaa, Chronic Comlications in patients with slowly progressing atutoimmune type 1 diabetes, Diabetes Care, vol. 22, 1999, p. 1347-1353.
Seijin-byou, The Journal of Adult Diseases, 2008, vol. 38, p. 438-444., abstract attached.
Fuguchi, Therapeutic Effects and Adverse Reactions to Oral Hypoglycemic Agents, Journal of the Nippon Hospital Pharmacists Assoc, 1976, vol. 1, p. 226-229, abstract only.
Colorcon (retrieved from website http://www.colorcon.com/products-formulation/all-products/film-coatings/immediate-release/opadry, published2015).
Bergmann, Decrease of serum dipeptidylpeptidase activity in severs sepsis patients, Clinica Chimica Acta 2002., p. 123-126.
Gallwitz, Safety and Efficacy of linagliptin in type 2 diabetes patients with common renal and cardiovascular risk factors, vol. 4,2013.
Groop, Effects of the DPP-4inhibitor linagliptin on albuminuria in patients with type 2 diabetes, www.abstractsonline.com, 2013.
Cooper, Kidney Disease End Points in a Pooled Analysis of individual Patient-Level Data from a large Clinical Trials Program of the Dipeptyl Peptidase 4 Inhibitor Linagliptin in Type 2 Diabetes, vol. 66, American Journal of Kidney Diseases, 2015.
Hocher, Renal and Cardiac Effects of DPP4 in inhibitors from preclinical development to clinical research, Kidney and Blood Pressure Research, vol. 36, 2012, p. 65-84.
Von Eynatten, Efficacy and safety of linagliptin in type 2 diabetes subjects at high risk for renal and cardiovascular disease, vol. 12, 2013.
Seijin-byou, abstract, The Journal of Adult Diseases, 2008. , vol. 38.
Clinical Journal of Chinese Medicine, vol. 3, 2008, p. 360-364.
Clinical Trials.gov, Efficacy and Safety of Lingliptin in Elderly Patients with Type 2 Diabetes, Mar. 10, 2010, NCT01084005.
Barrara, Granulation, Handbook of Powder Technology, vol. 11, 2015.
Piatti, Long term Oral L- Arginine-Administration Improves Peripheral and Hepatic Insulin Sensitivity, Emerging Treatments and Technology, Diabestes Care, vol. 24, 2011.
Clinical Trials.gov, NCT00622284, Efficacy and Safety of BI 1356 in Combination with Metformin in Patients with Type 2 Diabetes, 2013.
Kleeman, Pharmaceutical Substances, Synthesesm Patents, Applications, p. 1196-1997, 1999.
Rowe, Handbook of Pharmaceutical Excipients, Fifth Ed., Calcium Bicarbonate, 2006.
Clinical Trials.gov, Efficacy and Safety of BI 1356 in Combination with Metformin in Patients with Type 2 Diabetes, NCT00309608, 2006.
Clinical Trials.gov, 52-week add-on to metformin comparison of saxagliptin and sulphonurea, NCT00575588, 2007.
Walsh, Pharmaceutical Biotechnology,Ovewview of Protein structure, 2007.
Katdare, Excipient Development for Pharmaceutical Biotechnology and Drug Delivery Systems, Ten of the most common Neutralizers Used, 2006.
Remington , The Science of Pharmacy, 22nd Ed., Pharmacuetical Dosage Forms, 2013.
Lide, CRC Handbook of Chem and Physics, Disassociation Constants of Organic Acids and Bases, 2002, 82nd Ed.
Stahl, Handbook of Pharmaceutical Salts, Properties, Selection and Use, 2002.

Related Publications (1)

	Number	Date	Country
	20200055856 A1	Feb 2020	US

Continuations (7)

	Number	Date	Country
Parent	16373971	Apr 2019	US
Child	16662406		US
Parent	15725426	Oct 2017	US
Child	16373971		US
Parent	15285871	Oct 2016	US
Child	15725426		US
Parent	14994578	Jan 2016	US
Child	15285871		US
Parent	14462654	Aug 2014	US
Child	14994578		US
Parent	13563767	Aug 2012	US
Child	14462654		US
Parent	11744700	May 2007	US
Child	13563767		US

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