IP Library Granted Patent US 9,394,349
Granted Patent B2
US 9,394,349 · App. 13/843,773 · Granted Jul 19, 2016

Modification and compositions of human secretoglobin proteins

Inventors: Aprile L. Pilon (Rockville, MD); Humcha K. Hariprakasha (Rockville, MD); Richard S. Clayton (Rockville, MD); Melissa E. Winn (Rockville, MD)
Assignee: Therabron Therapeutics, Inc.
C07K14/47
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Quick Facts
Patent No.
US 9,394,349
App. No.
13/843,773
Granted
Jul 19, 2016
Kind
B2
Abstract

Novel compositions of recombinant human CC10 protein have been generated by chemically modifying the pure protein in vitro. Several new synthetic preparations containing isoforms of chemically modified CC10 have been generated by processes that utilize reactive oxygen species and reactive nitrogen species. These preparations contain novel isoforms of CC10 which have been characterized with enhanced or altered biological properties compared to the unmodified protein. Preparations containing novel isoforms may be used as standards to identify and characterize naturally occurring isoforms of native CC10 protein from blood or urine and ultimately to measure new CC10-based biomarkers to assess patient disease status. These preparations may also be used to treat respiratory, autoimmune, inflammatory, and other medical conditions that are not effectively treated with the unmodified protein.

Claims (180)

1. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more nitrotyrosines.

2. The composition of claim 1 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

3. The composition of claim 1 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more chlorotyrosines or di-tyrosines.

4. The composition of claim 1 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

5. The composition of claim 1 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

6. The composition of claim 1 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines or pyrrolidines.

7. The composition of claim 1 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

8. The composition of claim 1 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

9. The composition of claim 1 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

10. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more chlorotyrosines.

11. The composition of claim 10 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

12. The composition of claim 10 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines or di-tyrosines.

13. The composition of claim 10 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

14. The composition of claim 10 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

15. The composition of claim 10 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines or pyrrolidines.

16. The composition of claim 10 wherein the chemically or enzymatically synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

17. The composition of claim 10 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

18. The composition of claim 10 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

19. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more di-tyrosines.

20. The composition of claim 19 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

21. The composition of claim 19 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines or chlorotyrosines.

22. The composition of claim 19 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

23. The composition of claim 19 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

24. The composition of claim 19 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines or pyrrolidines.

25. The composition of claim 19 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic serniaidehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

26. The composition of claim 19 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

27. The composition of claim 19 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

28. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more cysteine glutathiolates.

29. The composition of claim 28 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

30. The composition of claim 28 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, or di-tyrosines.

31. The composition of claim 28 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more HNE-cysteines.

32. The composition of claim 28 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

33. The composition of claim 28 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines or pyrrolidines.

34. The composition of claim 28 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

35. The composition of claim 28 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

36. The composition of claim 28 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

37. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more HNE-cysteines.

38. The composition of claim 37 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

39. The composition of claim 37 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, or di-tyrosines.

40. The composition of claim 37 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates.

41. The composition of claim 37 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

42. The composition of claim 37 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines or pyrrolidines.

43. The composition of claim 37 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

44. The composition of claim 37 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

45. The composition claim 37 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

46. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more hydroxyprolines.

47. The composition of claim 46 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

48. The composition of claim 46 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, or di-tyrosines.

49. The composition of claim 46 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

50. The composition of claim 46 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

51. The composition of claim 46 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more pyrrolidines.

52. The compositlon of claim 46 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

53. The composition of claim 46 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

54. The composition claim 46 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

55. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more pyrrolidines.

56. The composition of claim 55 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

57. The composition of claim 55 wherein the chemically or enzymatically oxidized synthetic, CC10 further comprises one or more nitrotyrosines, chlorotyrosines, or di-tyrosines.

58. The composition of claim 55 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

59. The composition of claim 55 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

60. The composition of claim 55 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

61. The composition of claim 55 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

62. The composition of claim 55 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

63. The composition claim 55 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

64. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more α-aminoadipic semialdehydes.

65. The composition of claim 64 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

66. The composition of claim 64 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, or di-tyrosines.

67. The composition of claim 64 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

68. The composition of claim 64 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

69. The composition of claim 64 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxprolines.

70. The composition of claim 64 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

71. The composition of claim 64 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

72. The composition of claim 64 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

73. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more chloramines.

74. The composition of claim 73 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

75. The composition of claim 73 wherein the chemically or enzymatically oxidized synthetic, CC10 further comprises one or more nitrotyrosines, chlorotyrosines, or di-tyrosines.

76. The composition of claim 73 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

77. The composition of claim 73 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

78. The composition of claim 73 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

79. The composition of claim 73 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

80. The composition of claim 73 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

81. The composition claim 73 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

82. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more MDA-Lys.

83. The composition of claim 82 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

84. The composition of claim 82 wherein the chemically or enzymatically oxidized synthetic, CC10 further comprises one or more nitrotyrosines, chlorotyrosines, di-tyrosines.

85. The composition of claim 82 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

86. The composition of claim 82 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

87. The composition of claim 82 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

88. The composition of claim 82 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

89. The composition of claim 82 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3- ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

90. The composition of claim 82 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

91. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more HNE-Lys.

92. The composition of claim 91 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

93. The composition of claim 91 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, or di-tyrosines.

94. The composition of claim 91 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine gluathiolates or HNE-cysteines.

95. The composition of claim 91 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

96. The composition of claim 91 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

97. The composition of claim 91 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

98. The composition of claim 91 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

99. The composition of claim 91 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine car lysine residue.

100. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more acrolein-Lys.

101. The composition of claim 100 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

102. The composition of claim 100 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, or di-tyrosines.

103. The composition of claim 100 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

104. The composition of claim 100 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

105. The composition of claim 100 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

106. The composition of claim 100 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, NNE-Lys, carboxymethyllysines, or pHA-Lys.

107. The composition of claim 100 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

108. The composition of claim 100 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

109. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more carboxymethyllysines.

110. The composition of claim 109 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

111. The composition of claim 109 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, or di-tyrosines.

112. The composition of claim 109 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

113. The composition of claim 109 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

114. The composition of claim 109 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

115. The composition of claim 109 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, or pHA-Lys.

116. The composition of claim 109 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

117. The composition of claim 109 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

118. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more pHA-Lys.

119. The composition of claim 118 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

120. The composition of claim 118 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, or di-tyrosines.

121. The composition of claim 118 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

122. The composition of claim 118 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

123. The composition of claim 118 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

124. The composition of claim 118 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, or carboxymethyllysines.

125. The composition of claim 118 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

126. The composition of claim 118 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine car lysine residue.

127. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more 2-amino-3-ketobutyric acids.

128. The composition of claim 127 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

129. The composition of claim 127 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, or di-tyrosines.

130. The composition of claim 127 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

131. The composition of claim 127 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

132. The composition of claim 127 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

133. The composition of claim 127 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

134. The composition of claim 127 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more chloramines, valine peroxides, leucine peroxides, oxalic acids, pyruyic acids, or hydroxyphenylalanines.

135. The composition of claim 127 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

136. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more valine peroxides.

137. The composition of claim 136 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

138. The composition of claim 136 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, or di-tyrosines.

139. The composition of claim 136 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

140. The composition of claim 136 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

141. The composition of claim 136 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

142. The composition of claim 136 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

143. The composition of claim 136 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, leucine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

144. The composition of claim 136 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

145. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more leucine peroxides.

146. The composition of claim 145 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

147. The composition of claim 145 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, di-tyrosines.

148. The composition of claim 145 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

149. The composition of claim 145 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

150. The composition of claim 145 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

151. The composition of claim 145 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

152. The composition of claim 145 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, oxalic acids, pyruvic acids, or hydroxyphenylalanines.

153. The composition of claim 145 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

154. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more oxalic acids.

155. The composition of claim 154 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

156. The composition of claim 154 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, di-tyrosines.

157. The composition of claim 154 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

158. The composition of claim 154 wherein the chemically or enzymatically oxidized synthetic CC10 further compirses carbonyl groups in excess of those present in unmodified CC10.

159. The composition of claim 154 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

160. The composition of claim 154 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

161. The composition of claim 154 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, pyruvic acids, or hydroxyphenylalanines.

162. The composition of claim 154 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

163. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more pyruvic acids.

164. The composition of claim 163 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

165. The composition of claim 163 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, di-tyrosines.

166. The composition of claim 163 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more cysteine glutathiolates or HNE-cysteines.

167. The composition of claim 163 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

168. The composition of claim 163 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

169. The composition of claim 163 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

170. The composition of claim 163 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, or hydroxyphenylalanines.

171. The composition of claim 163 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

172. A composition of matter comprising a chemically or enzymatically oxidized synthetic CC10 having one or more hydroxyphenylalanines.

173. The composition of claim 172 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more methionine sulfoxides.

174. The composition of claim 172 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more nitrotyrosines, chlorotyrosines, di-tyrosines.

175. The composition of claim 172 wherein the chemically or enzymatically oxidized synthetic CC10further comprises one or more cysteine glutathiolates or HNE-cysteines.

176. The composition of claim 172 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises carbonyl groups in excess of those present in unmodified CC10.

177. The composition of claim 172 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more hydroxyprolines.

178. The composition of claim 172 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more α-aminoadipic semialdehydes, chloramines, MDA-Lys, HNE-Lys, acrolein-Lys, carboxymethyllysines, or pHA-Lys.

179. The composition of claim 172 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more 2-amino-3-ketobutyric acids, chloramines, valine peroxides, leucine peroxides, oxalic acids, or pyruvic acids.

180. The composition of claim 172 wherein the chemically or enzymatically oxidized synthetic CC10 further comprises one or more labels, chemicals, lipids, or peptides attached to a glutamine or lysine residue.

Assignments (2)
CHANGE OF NAME Recorded Apr 3, 2015
From: CLARASSANCE INC.
To: THERABRON THERAPEUTICS INC.
Reel/Frame 035365/0889 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 13, 2013
From: PILON, APRILE L.; HARIPRAKASHA, HUMCHA K.; CLAYTON, RICHARD S.; WINN, MELISSA E.
To: CLARASSANCE, INC.
Reel/Frame 031201/0755 →
Continuity (1)
Related Publication 20140275477A1 · Sep 18, 2014