Author: claimsbot

1. A composition comprising Compound I having the formula
wherein a portion of Compound I is present as polymorphic Form B characterized by one or more physical properties selected from the group consisting of:
(i) an X-ray powder diffraction pattern (CuK\u03b1) comprising diffraction peaks at about 12.5, 18.83 and 24.46\xb02\u03b8; and
(ii) a differential scanning calorimetry spectrum comprising a broad endotherm at about 100\xb0 C., and two other endotherms at about 138\xb0 C. and about 163\xb0 C.
2. The composition according to claim 1, wherein greater than 0.1% of Compound I (by weight) is present in the composition as Form B.
3. The composition according to claim 1, wherein greater than 1% of Compound I (by weight) is present in the composition as Form B.
4. The composition according to claim 1, wherein greater than 10% of Compound I (by weight) is present in the composition as Form B.
5. The composition according to claim 1, wherein greater than 50% of Compound I (by weight) is present in the composition as Form B.
6. A method for preparing a composition of Compound I according to claim 1 comprising crystallizing Compound I from a solvent selected from the group consisting of: (i) isopropanol, (ii) ethanol and water (95:5), (ii) isopropanol and water (88:12), (iii) tetrahydrofuran and water (9:1), and (iv) water.
7. A method for preparing a composition of Compound I according to claim 1 comprising adding dioxane to Compound I dissolved in water.
8. A pharmaceutical composition comprising a composition of Compound I according to claim 1, and one or more pharmaceutical carriers.
9. The pharmaceutical composition according to claim 8 that is adapted for administration via a route selected from the group consisting of oral, parenteral, topical, transdermal, and pulmonary.
10. The pharmaceutical composition according to claim 8 that is in an oral dosage form selected from the group consisting of pills, tablets, capsules, emulsions, suspensions, microsuspensions, wafers, sprinkles, chewing gum, powders, lyophilized powders, granules, and troches.
11. The pharmaceutical composition according to claim 8, wherein the polymorphic form of the Compound I is at least partially preserved for a period of time following administration.
12. A kit comprising:
a pharmaceutical composition according to claim 1; and
instructions which comprise one or more forms of information selected from the group consisting of indicating a disease state for which the composition is to be administered, storage information for the composition, dosing information and instructions regarding how to administer the composition.
13. The kit according to claim 12, wherein the kit comprises the composition in a multiple dose form.
14. An article of manufacture comprising:
a composition according to claim 1; and
packaging materials.
15. The article of manufacture according to claim 14, wherein the packaging material comprises a container for housing the composition.
16. The article of manufacture according to claim 15, wherein the container comprises a label indicating one or more members of the group consisting of a disease state for which the composition is to be administered, storage information, dosing information andor instructions regarding how to administer the composition.
17. The article of manufacture according to claim 14, wherein the composition is in a multiple dose form.
18. A method of inhibiting dipeptidyl peptidases comprising: causing a composition according to claim 1 to be present in a subject.
19. A method of treating a disease state for which dipeptidyl peptidases possess activity that contributes to the pathology andor symptomology of the disease state, the method comprising: administering a composition according to claim 1 to a subject in a therapeutically effective amount for the disease state.
20. The method according to claim 18, wherein the disease state is selected from the group consisting of type I diabetes, type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity; autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, psoriasis, and rheumatoid arthritis; AIDS; and cancers.
21. The method according to claim 18, wherein the disease state is selected from the group consisting of type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity.
22. The method according to claim 18, wherein the disease state is type II diabetes mellitus.
23. A composition comprising Compound I having the formula
wherein a portion of Compound I is present as polymorphic Form C characterized by an X-ray powder diffraction pattern (CuK\u03b1) comprising diffraction peaks at about 5.44 and 6.07\xb0 2\u03b8.
24. The composition according to claim 23, wherein greater than 0.1% of Compound I (by weight) is present in the composition as Form C.
25. The composition according to claim 23, wherein greater than 1% of Compound I (by weight) is present in the composition as Form C.
26. The composition according to claim 23, wherein greater than 10% of Compound I (by weight) is present in the composition as Form C.
27. The composition according to claim 23, wherein greater than 50% of Compound I (by weight) is present in the composition as Form C.
28. A method for preparing a composition of Compound I according to claim 23 comprising crystallizing Compound I from an isopropanol solution of Compound I.
29. A pharmaceutical composition comprising a composition of Compound I according to claim 23 and one or more pharmaceutical carriers.
30. The pharmaceutical composition according to claim 29 that is adapted for administration via a route selected from the group consisting of oral, parenteral, topical, transdermal, and pulmonary.
31. The pharmaceutical composition according to claim 29 that is in an oral dosage form selected from the group consisting of pills, tablets, capsules, emulsions, suspensions, microsuspensions, wafers, sprinkles, chewing gum, powders, lyophilized powders, granules, and troches.
32. The pharmaceutical composition according to claim 29, wherein the polymorphic form of the Compound I is at least partially preserved for a period of time following administration.
33. A kit comprising:
a pharmaceutical composition according to claim 29; and
instructions which comprise one or more forms of information selected from the group consisting of indicating a disease state for which the composition is to be administered, storage information for the composition, dosing information and instructions regarding how to administer the composition.
34. The kit according to claim 33, wherein the kit comprises the composition in a multiple dose form.
35. An article of manufacture comprising:
a composition according to claim 23; and
packaging materials.
36. The article of manufacture according to claim 35, wherein the packaging material comprises a container for housing the composition.
37. The article of manufacture according to claim 36, wherein the container comprises a label indicating one or more members of the group consisting of a disease state for which the composition is to be administered, storage information, dosing information andor instructions regarding how to administer the composition.
38. The article of manufacture according to claim 35, wherein the composition is in a multiple dose form.
39. A method of inhibiting dipeptidyl peptidases comprising: causing a composition according to claim 23 to be present in a subject.
40. A method of treating a disease state for which dipeptidyl peptidases possess activity that contributes to the pathology andor symptomology of the disease state, the method comprising: administering a composition according to claim 23 to a subject in a therapeutically effective amount for the disease state.
41. The method according to claim 40, wherein the disease state is selected from the group consisting of type I diabetes, type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity; autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, psoriasis, and rheumatoid arthritis; AIDS; and cancers.
42. The method according to claim 40, wherein the disease state is selected from the group consisting of type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity.
43. The method according to claim 40, wherein the disease state is type II diabetes mellitus.
44. A composition comprising Compound I having the formula
wherein a portion of Compound I is present as polymorphic Form D characterized by one or more physical properties selected from the group consisting of:
(i) an X-ray powder diffraction pattern (CuK\u03b1) comprising one diffraction peak at about 24.33\xb0 2\u03b8, and four other diffraction peaks selected from the group consisting of peaks at about 12.19, 16.71, 22.08, 22.88, and 23.27\xb0 2\u03b8;
(ii) an X-ray powder diffraction pattern (CuK\u03b1) comprising one diffraction peak at about 24.33\xb0 2\u03b8, and four other diffraction peaks selected from the group consisting of peaks at about 12.19, 14.04, 16.71, 17.75, 18.86, 19.96, 22.08, 22.88, 23.27, 25.02, 25.49, 26.03, and 27.99\xb0 2\u03b8; and
(ii) a differential scanning calorimetry spectrum comprising a broad endotherm centered at about 88\xb0 C. and two other endotherms at about 107\xb0 C. and 192\xb0 C.
45. The composition according to claim 44, wherein greater than 0.1% of Compound I (by weight) is present in the composition as Form D.
46. The composition according to claim 44, wherein greater than 1% of Compound I (by weight) is present in the composition as Form D.
47. The composition according to claim 44, wherein greater than 10% of Compound I (by weight) is present in the composition as Form D.
48. The composition according to claim 44, wherein greater than 50% of Compound I (by weight) is present in the composition as Form D.
49. A method for preparing a composition of Compound I according to claim 44, comprising adding acetonitrile to Compound I dissolved in water.
50. A pharmaceutical composition comprising a composition of Compound I according to claim 44, and one or more pharmaceutical carriers.
51. The pharmaceutical composition according to claim 50 that is adapted for administration via a route selected from the group consisting of oral, parenteral, topical, transdermal, and pulmonary.
52. The pharmaceutical composition according to claim 50 that is in an oral dosage form selected from the group consisting of pills, tablets, capsules, emulsions, suspensions, microsuspensions, wafers, sprinkles, chewing gum, powders, lyophilized powders, granules, and troches.
53. The pharmaceutical composition according to claim 50, wherein the polymorphic form of the Compound I is at least partially preserved for a period of time following administration.
54. A kit comprising:
a pharmaceutical composition according to claim 44, and
instructions which comprise one or more forms of information selected from the group consisting of indicating a disease state for which the composition is to be administered, storage information for the composition, dosing information and instructions regarding how to administer the composition.
55. The kit according to claim 54, wherein the kit comprises the composition in a multiple dose form.
56. An article of manufacture comprising:
a composition according to claim 44; and
packaging materials.
57. The article of manufacture according to claim 56, wherein the packaging material comprises a container for housing the composition.
58. The article of manufacture according to claim 57, wherein the container comprises a label indicating one or more members of the group consisting of a disease state for which the composition is to be administered, storage information, dosing information andor instructions regarding how to administer the composition.
59. The article of manufacture according to claim 56, wherein the composition is in a multiple dose form.
60. A method of inhibiting dipeptidyl peptidases comprising: causing a composition according to claim 44, to be present in a subject.
61. A method of treating a disease state for which dipeptidyl peptidases possess activity that contributes to the pathology andor symptomology of the disease state, the method comprising: administering a composition according to claim 44, to a subject in a therapeutically effective amount for the disease state.
62. The method according to claim 61, wherein the disease state is selected from the group consisting of type I diabetes, type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity; autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, psoriasis, and rheumatoid arthritis; AIDS; and cancers.
63. The method according to claim 61, wherein the disease state is selected from the group consisting of type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity.
64. The method according to claim 61, wherein the disease state is type II diabetes mellitus.
65. A composition comprising Compound I having the formula
wherein a portion of Compound I is present as polymorphic Form E characterized by one or more physical properties selected from the group consisting of:
(i) an X-ray powder diffraction pattern (CuK\u03b1) comprising diffraction peaks at about 13.10, 13.94, 17.15, and 21.27\xb02\u03b8;
(ii) an X-ray powder diffraction pattern (CuK\u03b1) comprising two diffraction peaks at about 21.27 and 17.15\xb0 2\u03b8, and three diffraction peaks selected from the group consisting ofpeaks at about 11.90, 12.66, 13.10, 13.59, 13.94, 17.54, 22.03, 22.61, 24.06, 24.70, 26.31, 27.34, and 31.10\xb0 2\u03b8; and
(iii) a differential scanning calorimetry spectrum comprising a forked endotherm that comprises peaks at about 107\xb0 C., about 110\xb0 C. and about 114\xb0 C.
66. The composition according to claim 65, wherein greater than 0.1% of Compound I (by weight) is present in the composition as Form E.
67. The composition according to claim 65, wherein greater than 1% of Compound I (by weight) is present in the composition as Form E.
68. The composition according to claim 65, wherein greater than 10% of Compound I (by weight) is present in the composition as Form E.
69. The composition according to claim 65, wherein greater than 50% of Compound I (by weight) is present in the composition as Form E.
70. A method for preparing a composition of Compound I according to claim 65, comprising: adding acetonitrile to Compound I dissolved in water.
71. A pharmaceutical composition comprising a composition of Compound I according to claim 65, and one or more pharmaceutical carriers.
72. The pharmaceutical composition according to claim 71 that is adapted for administration via a route selected from the group consisting of oral, parenteral, topical, transdermal, and pulmonary.
73. The pharmaceutical composition according to claim 71 that is in an oral dosage form selected from the group consisting of pills, tablets, capsules, emulsions, suspensions, microsuspensions, wafers, sprinkles, chewing gum, powders, lyophilized powders, granules, and troches.
74. The pharmaceutical composition according to claim 71, wherein the polymorphic form of the Compound I is at least partially preserved for a period of time following administration.
75. A kit comprising:
a pharmaceutical composition according to claim 70; and
instructions which comprise one or more forms of information selected from the group consisting of indicating a disease state for which the composition is to be administered, storage information for the composition, dosing information and instructions regarding how to administer the composition.
76. The kit according to claim 75, wherein the kit comprises the composition in a multiple dose form.
77. An article of manufacture comprising:
a composition according to claim 65; and
packaging materials.
78. The article of manufacture according to claim 77, wherein the packaging material comprises a container for housing the composition.
79. The article of manufacture according to claim 78, wherein the container comprises a label indicating one or more members of the group consisting of a disease state for which the composition is to be administered, storage information, dosing information andor instructions regarding how to administer the composition.
80. The article of manufacture according to claim 77, wherein the composition is in a multiple dose form.
81. A method of inhibiting dipeptidyl peptidases comprising: causing a composition according to claim 65, to be present in a subject.
82. A method of treating a disease state for which dipeptidyl peptidases possess activity that contributes to the pathology andor symptomology of the disease state, the method comprising: administering a composition according to claim 65, to a subject in a therapeutically effective amount for the disease state.
83. The method according to claim 82, wherein the disease state is selected from the group consisting of type I diabetes, type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity; autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, psoriasis, and rheumatoid arthritis; AIDS; and cancers.
84. The method according to claim 82, wherein the disease state is selected from the group consisting of type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity.
85. The method according to claim 82, wherein the disease state is type II diabetes mellitus.
86. A composition comprising Compound I having the formula
wherein a portion of Compound I is present as polymorphic Form F characterized by an X-ray powder diffraction pattern (CuK\u03b1) comprising diffraction peaks at about 12.39, 20.63, 26.03, and 30.05\xb02\u03b8.
87. The composition according to claim 86, wherein greater than 0.1% of Compound I (by weight) is present in the composition as Form F.
88. The composition according to claim 86, wherein greater than 1% of Compound I (by weight) is present in the composition as Form F.
89. The composition according to claim 86, wherein greater than 10% of Compound I (by weight) is present in the composition as Form F.
90. The composition according to claim 86, wherein greater than 50% of Compound I (by weight) is present in the composition as Form F.
91. A method of preparing a composition of Compound I according to claim 86 comprising: crystallizing Compound I from tetrahydrofuran and water solution of Compound I.
92. A pharmaceutical composition comprising a composition of Compound I according to claim 86, and one or more pharmaceutical carriers.
93. The pharmaceutical composition according to claim 92 that is adapted for administration via a route selected from the group consisting of oral, parenteral, topical, transdermal, and pulmonary.
94. The pharmaceutical composition according to claim 92 that is in an oral dosage form selected from the group consisting of pills, tablets, capsules, emulsions, suspensions, microsuspensions, wafers, sprinkles, chewing gum, powders, lyophilized powders, granules, and troches.
95. The pharmaceutical composition according to claim 92, wherein the polymorphic form of the Compound I is at least partially preserved for a period of time following administration.
96. A kit comprising:
a pharmaceutical composition according to claim 86; and
instructions which comprise one or more forms of information selected from the group consisting of indicating a disease state for which the composition is to be administered, storage information for the composition, dosing information and instructions regarding how to administer the composition.
97. The kit according to claim 96, wherein the kit comprises the composition in a multiple dose form.
98. An article of manufacture comprising:
a composition according to claim 86; and
packaging materials.
99. The article of manufacture according to claim 98, wherein the packaging material comprises a container for housing the composition.
100. The article of manufacture according to claim 99, wherein the container comprises a label indicating one or more members of the group consisting of a disease state for which the composition is to be administered, storage information, dosing information andor instructions regarding how to administer the composition.
101. The article of manufacture according to claim 98, wherein the composition is in a multiple dose form.
102. A method of inhibiting dipeptidyl peptidases comprising: causing a composition according to claim 86, to be present in a subject.
103. A method of treating a disease state for which dipeptidyl peptidases possess activity that contributes to the pathology andor symptomology of the disease state, the method comprising: administering a composition according to claim 86 to a subject in a therapeutically effective amount for the disease state.
104. The method according to claim 103, wherein the disease state is selected from the group consisting of type I diabetes, type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity; autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, psoriasis, and rheumatoid arthritis; AIDS; and cancers.
105. The method according to claim 103, wherein the disease state is selected from the group consisting of type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity.
106. The method according to claim 103, wherein the disease state is type II diabetes mellitus.
107. A composition comprising Compound I having the formula
wherein a portion of Compound I is present as polymorphic Form G characterized by an X-ray powder diffraction pattern (CuK\u03b1) comprising five or more diffraction peaks selected from the group consisting of diffraction peaks at about 13.22, 14.23, 18.62, 19.77, 24.36, 25.06, and 30.71\xb02\u03b8.
108. The composition according to claim 107, wherein greater than 0.1% of Compound I (by weight) is present in the composition as Form G.
109. The composition according to claim 107, wherein greater than 1% of Compound I (by weight) is present in the composition as Form G.
110. The composition according to claim 107, wherein greater than 10% of Compound I (by weight) is present in the composition as Form G.
111. The composition according to claim 107, wherein greater than 50% of Compound I (by weight) is present in the composition as Form G.
112. A method for preparing a composition of Compound I according to claim 107 comprising: crystallizing Compound I from a tetrahydrofuran and water solution of Compound I.
113. A pharmaceutical composition comprising a composition of Compound I according to claim 107, and one or more pharmaceutical carriers.
114. The pharmaceutical composition according to claim 113 that is adapted for administration via a route selected from the group consisting of oral, parenteral, topical, transdermal, and pulmonary.
115. The pharmaceutical composition according to claim 113 that is in an oral dosage form selected from the group consisting of pills, tablets, capsules, emulsions, suspensions, microsuspensions, wafers, sprinkles, chewing gum, powders, lyophilized powders, granules, and troches.
116. The pharmaceutical composition according to claim 113, wherein the polymorphic form of the Compound I is at least partially preserved for a period of time following administration.
117. A kit comprising:
a pharmaceutical composition according to claim 113; and
instructions which comprise one or more forms of information selected from the group consisting of indicating a disease state for which the composition is to be administered, storage information for the composition, dosing information and instructions regarding how to administer the composition.
118. The kit according to claim 117, wherein the kit comprises the composition in a multiple dose form.
119. An article of manufacture comprising:
a composition according to claim 107; and
packaging materials.
120. The article of manufacture according to claim 119, wherein the packaging material comprises a container for housing the composition.
121. The article of manufacture according to claim 120, wherein the container comprises a label indicating one or more members of the group consisting of a disease state for which the composition is to be administered, storage information, dosing information andor instructions regarding how to administer the composition.
122. The article of manufacture according to claim 119, wherein the composition is in a multiple dose form.
123. A method of inhibiting dipeptidyl peptidases comprising: causing a composition according to claim 107, to be present in a subject.
124. A method of treating a disease state for which dipeptidyl peptidases possess activity that contributes to the pathology andor symptomology of the disease state, the method comprising: administering a composition according to claim 107, to a subject in a therapeutically effective amount for the disease state.
125. The method according to claim 124, wherein the disease state is selected from the group consisting of type I diabetes, type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity; autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, psoriasis, and rheumatoid arthritis; AIDS; and cancers.
126. The method according to claim 124, wherein the disease state is selected from the group consisting of type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity.
127. The method according to claim 124, wherein the disease state is type II diabetes mellitus.
128. A composition comprising Compound I having the formula
wherein a portion of Compound I is present as Amorphous Form, characterized by one or more physical properties selected from the group consisting of:
(i) an XRPD diffraction pattern (CuK\u03b1) characterized by a broad halo with no discernable diffraction peak; and
(ii) a glass transition temperature at about 82\xb0 C. and an exotherm at about 138\xb0 C.
129. The composition according to claim 128, wherein greater than 0.1% of Compound I (by weight) is present in the composition as Amorphous Form.
130. The composition according to claim 128, wherein greater than 1% of Compound I (by weight) is present in the composition as Amorphous Form.
131. The composition according to claim 128, wherein greater than 5% of Compound I (by weight) is present in the composition as Amorphous Form.
132. The composition according to claim 128, wherein greater than 10% of Compound I (by weight) is present in the composition as Amorphous Form.
133. The composition according to claim 128, wherein greater than 50% of Compound I (by weight) is present in the composition as Amorphous Form.
134. The composition according to claim 128, wherein greater than 75% of Compound I (by weight) is present in the composition as Amorphous Form.
135. The composition according to claim 128, wherein greater than 90% of Compound I (by weight) is present in the composition as Amorphous Form.
136. The composition according to claim 128, wherein greater than 95% of Compound I (by weight) is present in the composition as Amorphous Form.
137. The composition according to claim 128, wherein greater than 97% of Compound I (by weight) is present in the composition as Amorphous Form.
138. The composition according to claim 128, wherein greater than 99% of Compound I (by weight) is present in the composition as Amorphous Form.
139. A method for preparing a composition of Compound I according to claim 128 comprising: lyophilizing a water solution of Compound I.
140. A pharmaceutical composition comprising a composition of Compound I according to claim 128, and one or more pharmaceutical carriers.
141. The pharmaceutical composition according to claim 140 that is adapted for administration via a route selected from the group consisting of oral, parenteral, topical, transdermal, and pulmonary.
142. The pharmaceutical composition according to claim 140 that is in an oral dosage form selected from the group consisting of pills, tablets, capsules, emulsions, suspensions, microsuspensions, wafers, sprinkles, chewing gum, powders, lyophilized powders, granules, and troches.
143. The pharmaceutical composition according to claim 140, wherein the polymorphic form of the Compound I is at least partially preserved for a period of time following administration.
144. A kit comprising:
a pharmaceutical composition according to claim 140; and
instructions which comprise one or more forms of information selected from the group consisting of indicating a disease state for which the composition is to be administered, storage information for the composition, dosing information and instructions regarding how to administer the composition.
145. The kit according to claim 144, wherein the kit comprises the composition in a multiple dose form.
146. An article of manufacture comprising:
a composition according to claim 128; and
packaging materials.
147. The article of manufacture according to claim 146, wherein the packaging material comprises a container for housing the composition.
148. The article of manufacture according to claim 147, wherein the container comprises a label indicating one or more members of the group consisting of a disease state for which the composition is to be administered, storage information, dosing information andor instructions regarding how to administer the composition.
149. The article of manufacture according to claim 146, wherein the composition is in a multiple dose form.
150. A method of inhibiting dipeptidyl peptidases comprising: causing a composition according to claim 128 to be present in a subject.
151. A method of treating a disease state for which dipeptidyl peptidases possess activity that contributes to the pathology andor symptomology of the disease state, the method comprising: administering a composition according to claim 128 to a subject in a therapeutically effective amount for the disease state.
152. The method according to claim 151, wherein the disease state is selected from the group consisting of type I diabetes, type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity; autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, psoriasis, and rheumatoid arthritis; AIDS; and cancers.
153. The method according to claim 151, wherein the disease state is selected from the group consisting of type II diabetes mellitus, diabetic dislipidemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose (IFG), metabolic acidosis, ketosis, appetite regulation and obesity.
154. The method according to claim 151, wherein the disease state is type II diabetes mellitus.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1. A leadframe comprising:
a base metal structure having first and second surfaces;
a first metal layer, adhesive to polymeric materials, adherent to said first surface; and
said second surface covered by a second metal layer for affinity to reflow metals, said second metal layer having a different composition from said first metal layer.
2. The leadframe according to claim 1 wherein said base metal is selected from a group consisting of copper, copper alloy, aluminum, iron-nickel alloy, and covar.
3. The leadframe according to claim 1 wherein said first metal layer comprises a nickel layer in contact with said base metal, a palladium layer in contact with said nickel layer, and an outermost tin layer in contact with said palladium layer.
4. The leadframe according to claim 1 wherein said first metal layer comprises a nickel layer in contact with said base metal, a palladium layer in contact with said nickel layer, a gold layer in contact with said palladium layer, and an outermost tin layer in contact with said gold layer.
5. The leadframe according to claim 1 wherein said first metal layer comprises a silver layer in contact with said base metal.
6. The leadframe according to claim 1 wherein said second metal layer comprises a nickel layer in contact with said base metal, a palladium layer in contact with said nickel layer, and an outermost gold layer in contact with said palladium layer.
7. A leadframe comprising:
a base metal structure having first and second surfaces;
said first surface oxidized to form an oxide layer of said base metal adhesive to polymeric materials; and
said a metal layer covering said second surface having affinity to reflow metals.
8. The leadframe according to claim 7 in which a silver layer covers selective areas on said first surface.
9. The leadframe according to claim 7 wherein said metal layer on said second surface comprises a nickel layer in contact with said base metal, a palladium layer in contact with said nickel layer, and an outermost gold layer in contact with said palladium layer.
10. A semiconductor device comprising:
a leadframe of a base metal with a first and second surface, a chip mount pad and a plurality of lead segments, each segment having a first end near said mount pad and a second end remote from said mount pad;
a first metal layer, adhesive to polymeric materials, adherent to said first surface; and said second surface covered by a second metal layer for affinity to reflow metals, said second metal layer having a different composition from said first metal layer;
a semiconductor chip attached to said mount pad;
bonding wires interconnecting said chip and said first ends of said lead segments; and
polymeric encapsulation material covering said chip, said bonding wires and said first ends of said lead segments.
11. The device according to claim 10 further comprising reflow metals on said second leadframe surface, selectively covering at least said second ends of said lead segments.
12. The device according to claim 10 wherein said leadframe is for QFN (Quad Flat No-leads) or for SON (Small Outline No-leads) packages.
13. The device according to claim 10 wherein said first metal layer comprises a nickel layer in contact with said base metal, a palladium layer in contact with said nickel layer, and an outermost tin layer in contact with said palladium layer.
14. The device according to claim 10 wherein said first metal layer comprises a nickel layer in contact with said base metal, a palladium layer in contact with said nickel layer, a gold layer in contact with said palladium layer, and an outermost tin layer in contact with said gold layer.
15. The device according to claim 10 wherein said first metal layer comprises a silver layer in contact with said base metal.
16. The device according to claim 10 wherein said second metal layer comprises a nickel layer in contact with said base metal, a palladium layer in contact with said nickel layer, and an outermost gold layer in contact with said palladium layer.
17. A semiconductor device comprising:
a leadframe of a base metal with a first and second surface, a chip mount pad and a plurality of lead segments, each segment having a first end near said mount pad and a second end remote from said mount pad;
said first surface oxidized to form an oxide layer of said base metal adhesive to polymeric materials with selective areas covered by a silver layer; and said second surface covered by a metal layer for affinity to reflow metals;
a semiconductor chip attached to said mount pad;
bonding wires interconnecting said chip and said first ends of said lead segments; and
polymeric encapsulation material covering said chip, said bonding wires and said first ends of said lead segments.
18. A method for fabricating a leadframe comprising the steps of:
providing a base metal structure having first and second surfaces;
preparing said first surface metallurgically so that it becomes adhesive to polymeric materials; and
preparing said second surface metallurgically so that so that it becomes affine to reflow metals.
19. The method according to claim 18 wherein said structure is suitable as a semiconductor device leadframe.
20. The method according to claim 18 wherein said metallurgical preparation comprises the steps of:
plating on said first and second surfaces consecutively a layer of nickel on said base metal and a layer of palladium on said nickel layer;
plating on said first surface a layer of tin on said palladium layer; and
plating on said second surface a layer of gold on said palladium layer.
21. The method according to claim 18 wherein said metallurgical preparation comprises the steps of:
plating on said first and second surfaces consecutively a layer of nickel on said base metal, a layer of palladium on said nickel layer, and a layer of gold on said palladium layer; and
plating on said first surface a layer of tin on said gold layer.
22. The method according to claim 18 wherein said metallurgical preparation comprises the steps of:
plating on said first surface selectively a layer of silver on said base metal; and
plating on said second surface consecutively a layer of nickel on said base metal, a layer of palladium on said nickel layer, and a layer of gold on said palladium layer.
23. The method according to claim 18 wherein said metallurgical preparation comprises the steps of:
oxidizing said first surface of said base metal;
plating a silver layer on selected areas of said base metal oxide; and
plating on said second surface consecutively a layer of nickel on said base metal, a layer of palladium on said nickel layer, and a layer of gold on said palladium layer.
24. The method according to claim 23 wherein said step of oxidizing is provided by unaided metal oxide growth or by stimulated metal oxide growth.
25. The method according to claim 18 wherein said step of preparing said second surface metallurgically is performed on exposed base metal portions after semiconductor devices have been assembled and encapsulated on said leadframe, said metallurgical preparation comprising the steps of:
plating on said exposed portions consecutively a layer of nickel on said base metal, a layer of palladium on said nickel layer, and a layer of gold on said palladium layer.

1. A lighting fixture comprising:
a front end-portion having an edge defining a light opening and a back end-portion spaced from the light opening which has a centerline;
at least one LED emitter on a substantially planar board disposed at the back end-portion for directing light toward the light opening, the emitter(s) being positioned off-centerline in a first lateral direction; and
a lens for the at least one emitter, the lens being configured for distribution of light from the emitter(s) primarily in a second lateral direction which is opposite the first lateral direction such that the light passes through the light opening at a portion of the edge that is off-centerline in the second lateral direction, thereby to widen the illumination angle from the fixture.
2. The recessed lighting fixture of claim 1 wherein no more than minimal light directed onto the support member.
3. The lighting fixture of claim 1 wherein each lens is a separate piece over the associated emitter.
4. The recessed lighting fixture of claim 1 wherein:
the board has a peripheral region surrounding a non-peripheral region; and
at least one other emitter on the non-peripheral region and having the associated lens configured for distribution of light therefrom along an emitter axis with no more than minimal light directed onto the support member.
5. The lighting fixture of claim 4 wherein the peripheral region has an annular shape concentric with the opening.
6. The lighting fixture of claim 1 wherein the mounting board is substantially parallel to a light-opening plane.
7. The lighting fixture of claim 1 wherein each lens for directing light in a preferential-side toward the second lateral direction includes:
an emitter-adjacent base end forming an opening;
an inner surface extending from the base end with (a) a surrounding lateral surface formed about the emitter axis and (b) an end surface configured to direct light toward the preferential side, the inner surface forming a void;
an output-end surface configured to direct light toward the preferential side; and
an outer lateral surface configured for TIR to direct light toward the output-end surface, whereby light from the emitter exits the output-end surface predominantly toward the preferential side.
8. The lighting fixture of claim 7 wherein the surrounding lateral surface is substantially cylindrical.
9. The lighting fixture of claim 8 wherein the substantially cylindrical lateral surface has a right cylindrical shape of substantially circular cross-section.
10. The lens of claim 7 wherein the inner end surface has a substantially planar portion angled toward the preferential side and transitioning from near the emitter axis to a convex portion that is on a non-preferential side and meets the surrounding lateral surface at a position farthest from the base end.
11. The lighting fixture of claim 10 wherein the outer lateral surface extends from the base end to terminate proximal to the output-end surface at distances from the emitter axis which are greatest on the preferential side and gradually decrease toward a non-preferential side.
12. The lighting fixture of claim 11 wherein the outer lateral surface has angles of divergence with respect to the emitter axis which are the greatest on the preferential side and gradually decrease toward the non-preferential side.
13. The lighting fixture of claim 7 wherein the output-end surface is substantially planar.
14. The lighting fixture of claim 13 wherein the emitter-adjacent base end is a planar surface which is substantially perpendicular to an emitter axis.
15. The lighting fixture of claim 14 wherein the output-end surface is angled toward a non-preferential side, with the edge of such output-end surface on the preferential side being farthest from the plane of the base end.
16. The lighting fixture of claim 7 wherein the lens further includes an outward flange about the outer lateral surface.
17. The lighting fixture of claim 16 wherein the outward flange includes a reference mark indicating an orientation of the preferential side during installation of the lens over the emitter.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1. A device (10) for damping torsion between a clutch element (16) and a transmission shaft, the device (10) comprising:
at least one input washer (12A, 12B) that is rotationally integral with the clutch element (16) around the axis (B) of the transmission shaft;
at least one output web (18A, 18B) that is rotationally integral with the transmission shaft by means of a central hub (20);
at least one pair of circumferentially acting elastic members (42) that are interposed circumferentially in series between the input washer (12A, 12B) and the output web (18A, 18B);
at least one phase washer (44) that is mounted rotatably around the axis (B) of the transmission shaft and is interposed circumferentially between the two elastic members (42) of said pair,
two output webs (18A, 18B) that are arranged axially on either side of each input washer (12A, 12B),

wherein the elastic members (42) are arranged in series on the circumference of a single circle having an axis (B).
2. The device (10) according to claim 1, wherein each input washer (12A, 12B) has a central orifice that is demarcated by an inner edge (34), the input washer (12A, 12B) being rotationally guided by sliding of its inner edge (34) on a cylindrical guidance face (36) that is rotationally integral with the central hub (20).
3. The device (10) according to claim 2, wherein the cylindrical guidance face (36) is implemented integrally with the central hub (20).
4. The device (10) according to claim 2, wherein the guidance face (36) has at least two radial stop faces (60, 62), each of which is capable of interacting with an associated radial stop face (69, 71) that extends from the inner edge (34) of the input washer (12A, 12B) in order to limit, in both directions, the rotation of the input washer (12A, 12B) with respect to the output web (18A, 18B).
5. The device (10) according to claim 1, wherein the phase washer (44) has a central orifice that is demarcated by an inner edge (46), the phase washer (44) being rotationally guided by sliding of its inner edge (46) on a cylindrical guidance face (36) that is rotationally integral with the central hub (20).
6. The device (10) according to claim 5 taken in combination with any one of claims 2 to 4, wherein the phase washer (44) and each input washer (12A, 12B) are rotationally guided by a common guidance face (36) that is integral with the central hub (20).
7. The device (10) according to claim 5, wherein the guidance face (36) has at least two radial stop faces (60, 62), each of which is capable of interacting with an associated radial stop face (72, 74) that extends from the inner edge (46) of the phase washer (44) in order to limit, in both directions, the rotation of the phase washer (44) with respect to the output web (18A, 18B).
8. The device (10) according to claim 7, wherein the two radial stop faces (60, 62) of the guidance face (36) are common to the phase washer (44) and to each input washer (12A, 12B).
9. The device (10) according to claim 8, wherein the two output webs (18A, 18B) are arranged axially on either side of each phase washer (44).
10. A pendulum-type damping device intended to be part of the torsion damping device according to claim 1, wherein it has at least one pair of pendulum flyweights mounted oscillatingly in a radial plane on a peripheral ring of the phase washer (44).
11. The device (10) according to claim 3, wherein the guidance face (36) has at least two radial stop faces (60, 62), each of which is capable of interacting with an associated radial stop face (69, 71) that extends from the inner edge (34) of the input washer (12A, 12B) in order to limit, in both directions, the rotation of the input washer (12A, 12B) with respect to the output web (18A, 18B).
12. The device (10) according to claim 2, wherein the phase washer (44) has a central orifice that is demarcated by an inner edge (46), the phase washer (44) being rotationally guided by sliding of its inner edge (46) on a cylindrical guidance face (36) that is rotationally integral with the central hub (20).
13. The device (10) according to claim 3, wherein the phase washer (44) has a central orifice that is demarcated by an inner edge (46), the phase washer (44) being rotationally guided by sliding of its inner edge (46) on a cylindrical guidance face (36) that is rotationally integral with the central hub (20).
14. The device (10) according to claim 4, wherein the phase washer (44) has a central orifice that is demarcated by an inner edge (46), the phase washer (44) being rotationally guided by sliding of its inner edge (46) on a cylindrical guidance face (36) that is rotationally integral with the central hub (20).
15. The device (10) according to claim 6, wherein the guidance face (36) has at least two radial stop faces (60, 62), each of which is capable of interacting with an associated radial stop face (72, 74) that extends from the inner edge (46) of the phase washer (44) in order to limit, in both directions, the rotation of the phase washer (44) with respect to the output web (18A, 18B).)
16. A pendulum-type damping device intended to be part of the torsion damping device according to claim 2, wherein it has at least one pair of pendulum flyweights mounted oscillatingly in a radial plane on a peripheral ring of the phase washer (44).
17. A pendulum-type damping device intended to be part of the torsion damping device according to claim 3, wherein it has at least one pair of pendulum flyweights mounted oscillatingly in a radial plane on a peripheral ring of the phase washer (44).
18. A pendulum-type damping device intended to be part of the torsion damping device according to claim 4, wherein it has at least one pair of pendulum flyweights mounted oscillatingly in a radial plane on a peripheral ring of the phase washer (44).
19. A pendulum-type damping device intended to be part of the torsion damping device according to claim 5, wherein it has at least one pair of pendulum flyweights mounted oscillatingly in a radial plane on a peripheral ring of the phase washer (44).
20. A pendulum-type damping device intended to be part of the torsion damping device according to claim 6, wherein it has at least one pair of pendulum flyweights mounted oscillatingly in a radial plane on a peripheral ring of the phase washer (44).
21. A pendulum-type damping device intended to be part of the torsion damping device according to claim 7, wherein it has at least one pair of pendulum flyweights mounted oscillatingly in a radial plane on a peripheral ring of the phase washer (44).
22. A pendulum-type damping device intended to be part of the torsion damping device according to claim 8, wherein it has at least one pair of pendulum flyweights mounted oscillatingly in a radial plane on a peripheral ring of the phase washer (44).
23. A pendulum-type damping device intended to be part of the torsion damping device according to claim 9, wherein it has at least one pair of pendulum flyweights mounted oscillatingly in a radial plane on a peripheral ring of the phase washer (44).