Modulators of complement activation: A patent review (2008-2013)

Expert Opinion on Therapeutic Patents

Volumn 24, Issue 6, 2014, Pages 665-686

  Larghi, Enrique L ^a   Kaufman, Teodoro S ^a  

^a UNIVERSIDAD NACIONAL DE ROSARIO   (Argentina)

Author keywords

Alternative pathway; Aptamers; Chimeric proteins; Classical pathway; Complement inhibitors; Complement therapeutics; Complement mediated diseases; Lectin pathway; Natural products; Specific monoclonal antibodies

Indexed keywords

CHIMERIC ANTIBODY; CHIMERIC PROTEIN; CLASSICAL COMPLEMENT PATHWAY C3 C5 CONVERTASE; COMPLEMENT; COMPLEMENT COMPONENT C1S INHIBITOR; COMPLEMENT COMPONENT C5 INHIBITOR; CYCLOPEPTIDE; LECTIN; NATURAL PRODUCT; PEPTIDOMIMETIC AGENT; POLYSACCHARIDE; PROTEIN DERIVATIVE; COMPLEMENT INHIBITOR;

ALZHEIMER DISEASE; CARDIOPULMONARY BYPASS; CEREBROVASCULAR ACCIDENT; COMPLEMENT ACTIVATION; COMPLEMENT ALTERNATIVE PATHWAY; COMPLEMENT CLASSICAL PATHWAY; COMPLEMENT DEFICIENCY; COMPLEMENT INHIBITION; COMPLEMENT SYSTEM; GLOMERULONEPHRITIS; HEART INFARCTION; HEMODIALYSIS; HUMAN; MACROMOLECULE; MEDICINAL CHEMISTRY; MOLECULAR WEIGHT; MULTIPLE SCLEROSIS; MYASTHENIA GRAVIS; NONHUMAN; PATENT; PROTEIN PROTEIN INTERACTION; REGULATORY MECHANISM; REVIEW; RHEUMATOID ARTHRITIS; ANIMAL; DRUG DEVELOPMENT; DRUG EFFECTS; PHYSIOLOGY;

ANIMALS; COMPLEMENT ACTIVATION; COMPLEMENT INACTIVATING AGENTS; COMPLEMENT SYSTEM PROTEINS; DRUG DISCOVERY; HUMANS; PATENTS AS TOPIC;

EID: 84901279958     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2014.898063     Document Type: Review

References (201)

1. Emlen W, Li W, Kirschfink M. Therapeutic complement inhibition: New developments. Semin Thromb Hemost 2010;36:660-8
2. Dodds AW, Matsushita M. The phylogeny of the complement system and the origins of the classical pathway. Immunobiology 2007;212:233-43 (Pubitemid 46825238
3. Mastellos D, Andronis C, Persidis A, Lambris JD. Novel biological networks modulated by complement. Clin Immunol 2005;115:225-35 (Pubitemid 40712318
4. Sarma JV, Ward PA. The complement System. Cell Tissue Res 2011;343:227-35
5. Doni A, Garlanda C, Bottazzi B, et al. Interactions of the humoral pattern recognition molecule PTX3 with the complement system. Immunobiology 2012;217:1122-8
6. Ali YM, Kenawy HI, Muhammad A, et al. Human L-ficolin, a recognition molecule of the lectin activation pathway of complement, activates complement by binding to pneumolysin, the major toxin of streptococcus pneumoniae. PLoS One 2013;8:e0082583
7. Thrane AS, Skehan JD, Thrane PS. A novel interpretation of immune redundancy and duality in reperfusion injury with important implications for intervention in ischaemic disease. Med Hypotheses 2007;68:1363-70 (Pubitemid 46498444
8. Van Der Pol P, Schlagwein N, van Gijlswijk DJ, et al. Mannan-binding lectin mediates renal ischemia/reperfusion injury independent of complement activation. Am J Transplant 2012;12:877-87
9. Leinhase I, Rozanski M, Harhausen D, et al. Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: A randomized placebo-controlled study in mice. J Neuroinflammation 2007;4:13
10. Bexborn F, Andersson PO, Chen H, et al. The tick-over theory revisited: Formation and regulation of the soluble alternative complement C3 convertase (C3(H(2)O)Bb). Mol Immunol 2008;45:2370-9
11. Hourcade DE. The role of properdin in the assembly of the alternative pathway of C3 convertases of complement. J Biol Chem 2006;281:2128-32 (Pubitemid 43845802
12. Alcorlo M, Tortajada A, Rodríguez de Córdoba S, et al. Structural basis for the stabilization of the complement alternative pathway C3 convertase by properdin. Proc Natl Acad Sci USA 2013;110:13504-9
13. Harboe M, Mollnes TE. The alternative complement pathway revisited. J Cell Mol Med 2008;12:1074-84
14. Rawal N, Rajagopalan R, Salvi VP. Activation of complement component C5: Comparison of C5 convertases of the lectin pathway and classical pathway of complement. J Biol Chem 2008;283:7853-63
15. Pangburn MK, Rawal N. Structure and function of complement C5 convertase enzymes. Biochem Soc Trans 2002;30:1006-10 (Pubitemid 36002396
16. Zipfel PF, Skerka C. Complement regulators and inhibitory proteins. Nat Rev Immunol 2009;9:1-12
17. Rambach G, Würzner R, Speth C. Complement: An efficient sword of innate immunity. Contrib Microbiol 2008;15:78-100
18. Larghi EL, Kaufman TS. Isolation, synthesis and complement inhibiting activity of the naturally occurring K-76, its analogues and derivatives. ARKIVOC 2011;vii:49-102
19. Rawal N, Rajagopalan R, Salvi VP. Stringent regulation of complement lectin pathway C3/C5 convertase by C4b-binding protein (C4BP). Mol Immunol 2009;46:2902-10
20. Frank MM. Complement disorders and hereditary angioedema. J Allergy Clin Immunol 2010;125:S262-71
21. Truedsson L, Bengtsson AA, Sturfelt G. Complement deficiencies and systemic lupus erythematosus. Autoimmunity 2007;40:560-6 (Pubitemid 350302182
22. Chen M, Daha MR, Kallenberg CG. The complement system in systemic autoimmune disease. J Autoimmun 2010;34:J276-86
23. Füst A, Csuka D, Imre L, et al. The role of complement activation in the pathogenesis of Fuchs' dystrophy. Mol Immunol 2014;58:177-81
24. Ballanti E, Perricone C, Greco E, et al. Complement and autoimmunity. Immunol Res 2013;56:477-91
25. Gorbet MB, Sefton MV. Biomaterial-Associated thrombosis: Roles of coagulation factors, complement, platelets and leukocytes. Biomaterials 2004;25:5681-703 (Pubitemid 38624449
26. Noris M, Remuzzi G. Overview of complement activation and regulation. Semin Nephrol 2013;33:479-92
27. Holers VM. The spectrum of complement alternative pathwaymediated diseases. Immunol Rev 2008;223:300-16 (Pubitemid 351986186
28. Craig TJ, Rojavin MA, Machnig T, et al. Effect of time to treatment on response to C1 esterase inhibitor concentrate for hereditary angioedema attacks. Ann Allergy Asthma Immunol 2013;111:211-15
29. Subasinghe NL, Khalil E, Travins JM, et al. Design and synthesis of polyethylene glycol-modified biphenylsulfonyl-Thiophenecarboxamidine inhibitors of the complement component C1s. Bioorg Med Chem Lett 2012;22:5303-7
30. Sonkar GK, Usha SRG. Study on the role of humoral immunity in renal transplant rejections and its correlation with histopathological findings. Saudi J Kidney Dis Transpl 2011;22:901-10
31. Chen G, Chen S, Chen X. Role of complement and perspectives for intervention in transplantation. Immunobiology 2013;218:817-27
32. Langlois PF, Gawryl MS. Complement activation occurs through both classical and alternative pathways prior to onset and resolution of adult respiratory distress syndrome. Clin Immunol Immunopathol 1988;47:152-63
33. Spirig R, Gajanayake T, Korsgren O, et al. Low molecular weight dextran sulfate as complement inhibitor and cytoprotectant in solid organ and islet transplantation. Mol Immunol 2008;45:4084-94
34. Imai N, Nishi S, Alchi B. Immunohistochemical evidence of activated lectin pathway in kidney allografts with peritubular capillary C4d deposition. Nephrol Dial Transplant 2006;21:2589-95 (Pubitemid 44644536
35. Farrar CA, Asgari E, Schwaeble W, et al. Which pathways trigger the role of complement in ischaemia/reperfusion injury? Front Immunol 2012;3:341
36. Burwick RM, Fichorova RN, Dawood HY, et al. Urinary excretion of C5b-9 in severe preeclampsia: Tipping the balance of complement activation in pregnancy. Hypertension 2013;62:1040-5
37. Sacks S, Karegli J, Farrar CA, et al. Targeting complement at the time of transplantation. Adv Exp Med Biol 2013;735:247-55
38. Schwertz H, Carter JM, Russ M, et al. Serine protease inhibitor nafamostat given before reperfusion reduces inflammatory myocardial injury by complement and neutrophil inhibition. J Cardiovasc Pharmacol 2008;52:151-60
39. Pedroni SM, Gonzalez JM, Wade J, et al. Complement inhibition and statins prevent fetal brain cortical abnormalities in a mouse model of preterm birth. Biochim Biophys Acta 2014;1842:107-15
40. Murata K, Baldwin WM III. Mechanisms of complement activation, C4d deposition, and their contribution to the pathogenesis of antibody-mediated rejection. Transplantat Rev (Orlando) 2009;23:139-50
41. Frangogiannis NG. The immune system and cardiac repair. Pharmacol Res 2008;58:88-111
42. Lambris JD. Current topics in complement II. Springer, New York; 2008
43. Arumugam TV, Woodruff TM, Lathia JD, et al. Neuroprotection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience 2009;158:1074-89
44. Holers MV. The complement system as a therapeutic target in autoimmunity. Clin Immunol 2003;107:140-51
45. van Werkhoven MB, Damman J, Van Dijk MC, et al. Complement mediated renal inflammation induced by donor brain death: Role of renal C5a-C5aR interaction. Am J Transplant 2013;13:875-82
46. Varga L, Farkas H. rhC1INH: A new drug for the treatment of attacks in hereditary angioedema caused by C1-inhibitor deficiency. Expert Rev Clin Immunol 2011;7:143-53
47. Gál P, Dobó J, Beinrohr L, et al. Inhibition of the serine proteases of the complement system. Adv Exp Med Biol 2013;735:23-40
48. Yang K, DeAngelis RA, Reed JE, et al. Complement in action: An analysis of patent trends from 1976 through 2011. Adv Exp Med Biol 2013;734:301-13
49. Munro HS. Treatment of inflammation and the complement and kinin cascades in a patient, particularly in chronic ulcerous skin lesions. US143478; 2010
50. Shepard AR, Clark AF, Klimko PG, Wax MB. Complement C1q inhibitors for the prevention and treatment of glaucoma. US117098; 2009
51. Christadoss P, Tuzun E. Methods and materials for treating autoimmune diseases and conditions. US7923010; 2011
52. Ali F, Gushue J, Meegalla S, et al. Thiophene amidines, compositions thereof, and methods of treating complement-mediated diseases and conditions. MY137509; 2009. US234081; 2005
53. Subasinghe NL, Ballentine S, Travins JM, et al. Thiophene sulfoximines, compositions thereof, and methods of treating complementmediated diseases and conditions. US7868023; 2011
54. Nalin S, Ehab K, Farah A, et al. Conjugated complement cascade inhibitors. MY138732; 2009. US004031; 2005
55. Fung MSC, Sun CRY, Sun WNC. Complement inhibitors and uses thereof. US8221756; 2012
56. Kotwal GJ, Arason GJ. Methods for treatment or prophylaxis of atherosclerosis and reperfusion injury. US200645; 2008
57. Garred P, Glue HT, Skjodt M-O. MASP isoforms as inhibitors of complement activation. US282285; 2012
58. Garred P, Glue TH. Therapeutic targeting of ficolin-3. WO000471; 2013
59. Stahl GL. Methods and compositions for the regulation of LCP (LCP)-Associated complement activation in hyperglycemic myocardial damage. US293524; 2011
60. Gal P, Zavodszky P, Ambrus-Aikelin G. Folded recombinant catalytic fragments of multidomain serine proteases, preparation and uses thereof. US042248; 2009
61. Krishna NK, Cunnion K. Methods for regulating complement cascade proteins using astrovirus coat protein and derivatives thereof. US058972; 2013. US055106; 2010
62. Krishna NK, Cunnion KM. Peptide compounds to regulate the complement system. US244924; 2013
63. Fung SC. Methods for preventing and treating tissue damage associated with ischemia-reperfusion injury. US0017031; 2009
64. Jensenius JC, Thiel S. MASP 2, a complement-fixing enzyme and uses for it. US8551790; 2013
65. Willis AC, Schwaeble H-W, Stover CM. MASP-2, a complement fixing enzyme, and uses for it. US219965; 2012
66. Dudler T, Gombotz WR, Brian J, et al. Compositions for inhibiting MASP-2 dependent complement activation. US282263; 2012
67. Schwaeble H-W, Stover CM, Tedford CE, et al. Methods for treating conditions associated with MASP-2 dependent complement activation. US258095; 2012
68. Demopulos GA, Schwaeble H-W, Tedford CE, Parent JB. Methods for treating conditions associated with MASP-2 dependent complement activation. US266559; 2013
69. Demopulos GA, Dudler T, Schwaeble H-W. Methods for treating conditions associated with MASP-2 dependent complement activation. US266560; 2013
70. Proudfoot A, Antonsson B, Kontula L, et al. Use of an immunoglobulin domain-containing cell surface recognition molecule for treating diseases. US193414; 2008
71. Schwaeble H-W, Demopulos GA. Compositions and methods of inhibiting MASP-1 and/or MASP-3 for the treatment of paroxysmal nocturnal hemoglobinuria. WO180834; 2013
72. O'brien G, Pike RN, Dean MM, et al. Mannose binding lectin and uses thereof. NZ535600; 2008. WO090774; 2003
73. Rekha B. Methods and compositions of inhibiting complement and cellular activation with dextran sulfate. US087393; 2010
74. Chen D, Zhang T, Zhang Y. Plant polysaccharide and preparation method and use thereof. CN101390868; 2009
75. Fung MSC, Sun WNC, Sun CRY. Anti-factor D antibodies and methods of treatment. US8124090; 2012
76. An LL, Fung C, Kelley RF, et al. Methods of treating with anti factor D antibodies. US8187604; 2012
77. Hass P, Jianping Y, Katschke K Jr, et al. Prevention and treatment of complement-Associated eye conditions. US0302333; 2013
78. Fung MSC, Yao Z. Use of complement pathway inhibitors to treat ocular diseases. US214538; 2009
79. Huang AJ, Kelley RF, Lowman H, et al. Humanized anti-factor D antibodies and uses thereof. SG189756; 2009. US269338; 2009
80. An LL, Fung SC, Kelley RF, et al. Humanized anti-factor D antibodies and uses thereof. AU200988; 2013. US171070; 2013
81. Altmann E, Hommel U, Lorthiois ELJ, et al. Complement pathway modulators and uses thereof. US295884; 2012
82. Romano C. Treatment of age-related macular degeneration using inhibitors of complement factor D. US269318; 2008
83. Rekha B. Anti-properdin antibodies. US8435512; 2013
84. Holers VM, Thurman JM, Tomlinson S, Stahel PF. Method for using inhibition of ACP in formulation for treatment of traumatic brain injury, spinal cord injury. JP162543; 2012. US292141; 2006
85. Song W. Anti-properdin antibodies and uses thereof. WO006449; 2013
86. Fung SC, Yao Z. Use of complement pathway inhibitors to treat ocular diseases. AU200223; 2013
87. Juo SH, Chou W-W, Wu JM, Liang CL. Method of modulating complement factor B (CFB) expression in cells. US245108; 2012
88. Adams CM, Babu C, Capparelli MP, et al. Complement Pathway modulators and uses thereof. US296377; 2013
89. Chen C, Kaleko M, Li B, et al. Complement factor B analogs and their uses. CA2833931; 2012
90. Van Lookeren Campagne M, Deforge L. Anti-factor B antibodies and their uses. US230997; 2012
91. Holers VM, Thurman JM, Taube C, et al. lnhibition of factor B, the ACP and methods related thereto. EP2340850; 2011
92. Emlen W, Holers VM, Flynn P. Humaneered anti-factor B antibody. US7964705; 2011
93. Rekha B. Method of inhibiting complement activation with factor Bb specific antibodies. US239573; 2010
94. Rekha B. Method of inhibiting complement activation with factor Ba specific antibodies and use thereof. US015139; 2010
95. Bansal R. Humanized and chimeric anti-factor bb antibodies and uses thereof. WO152020; 2013
96. Taylor RP, Dilillo DJ, Lindorfer MA, Pawluczkowycz AW. Compositions and methods for regulating the ACP of complement. US004183; 2009
97. Kolln J, Spillner E, Bredehorst R. Complement depletion using recombinant human C-3 derivatives. US270324; 2009
98. Vogel C-W, Fritzinger DC. Human complement C3 derivates with cobra venom factor-like function. US234191; 2008
99. Rooijakkers SHM, Van Wamel WJB, Van Kessel CPM, Van Strijp JAG. Therapeutic use of SCIN, a staphylococcal complement inhibitor in inflammatory diseases. US246175; 2009
100. Lambris JD, Geisbrecht BV. Secreted Staphylococcus aureus proteins and peptides for use in inhibiting activation of the complement system. US046075; 2011
101. De Silva A, Tyson K, Fikrig E. Ixodes scapularis salivary proteins and methods of use for modulation of the alternative complement pathway. US014218; 2011
102. McGeer PL, Lee M, Guo J-P, et al. Selective inhibition of the membrane attack complex of complement and C3 convertase by low molecular weight components of the aurin tricarboxylic acid synthetic complex. US035392; 2013
103. Lambris JD, Janssen B, Gros P. Structure of compstatin-C3 complex and use for rational drug design. WO153963; 2008
104. Lambris JD, Taylor FB, Lupu F, Kinasewitz G. Treatment of sepsis using complement inhibitors. US053302; 2013
105. Lambris JD, Taylor FB, Lupu F, et al. Treatment of sepsis using complement inhibitors. WO106635; 2011
106. Francois C, Deschatelets P. Methods of treating chronic disorders with complement inhibitors. WO178083; 2012
107. Francois C, Deschatelets P, Olson P. Local complement inhibition for treatment of complement-mediated disorders. US8580735; 2013
108. Francois C, Deschatelets P, Olson P. Compositions and methods for treatment of trauma. WO015087; 2009
109. Francois C, Deschatelets P. Compstatin analogs for treatment of rhinosinusitis and nasal polyposis. US324482; 2013
110. Pecht I, Erdei A, Eitan A. Complement C3a derived dimeric peptides and uses thereof. US306561; 2011
111. Bansal R. Humanized and chimeric anti-factor C3 antibodies and uses thereof. WO152024; 2013
112. Bansal R. Method of inhibiting complement activation with human anti-factor C3 antibodies and use thereof. US288493; 2012
113. Lambris JD, Schmidt C, Ricklin D. Regulator of complement activation and uses thereof. WO142362; 2013
114. Ashkenazi A, Fong S, Goddard A, et al. Treatment of complement-Associated disorders. US0189626; 2012
115. Shi H, Millis AJT, Nishikawa K, Mallik PK. Aptamer modulators of complement protein C3 and biologically active proteolytic products thereof. US141382; 2012
116. Etemad-Gilbertson B, Guild BC, Kim Y-I, et al. Compositions and methods for antibodies targeting complement protein C3b. US291106; 2010
117. Van Lookeren Campagne M. C3b antibodies and methods for the prevention and treatment of complement-Associated disorders. US128674; 2012
118. Holers VM, Thurman JM, Kulik L. Antibodies to the C3d fragment of complement component 3. US129728; 2013
119. Bansal R. Method of inhibiting complement activation with human antifactor C3 antibodies and use thereof. US288493; 2012
120. Lambris JD, Rafail S. Wound healing using complement inhibitors. WO174055; 2012
121. Lambris JD, Nadeau J, Doerner S, Berger NA. Treatment of colon cancer using complement inhibitors. WO135624; 2012
122. Lambris JD, Sander CE. Complement inhibitors for treatment of injury form intracerebral hemorrhage. US256136; 2011
123. Lambris JD, Ritis K. Method of inhibiting biomaterial-induced procoagulant activity using complement inhibitors. US8445190; 2013
124. Heinrich H-W. Immuno-Adsorbers for treatment of inflammations. US255344; 2008
125. Bell L, Rother RP. Treatment of paroxysmal nocturnal hemoglobinuria patients by an inhibitor of complement. AU206214; 2013. US237515; 2012
126. Gies D, Hunter JW, Springhorn JP. Polypeptides that bind to human complement component C5. US273052; 2013
127. Rother RP, Wang H, Zhong Z. Prolongation of survival of an allograft by inhibiting complement activity. AU200641; 2013
128. Diefenbach-Streiber B, Eberth A, Guild BC, et al. Compositions and methods for antibodies targeting complement protein C5. US064836; 2013
129. Roguska M, Keating MT, Guild BC, et al. Antigens and uses thereof. US166748; 2010
130. Yi W. Method of treating of asthma using antibody to complement component C5. JP215674; 2010
131. Evans MJ, Matis L, Mueller E, et al. Anti-C5 antibodies and their therapeutic uses. EP2270047; 2011
132. Rother RP, Halstead S, Willison H. Method and compositions for the treatment of antibody mediated neuropathies. US143343; 2010
133. Rother RP, Wang H, Lao A. Prolongation of survival of an allograft by inhibiting complement activity. US028850; 2009
134. Fung M, Lu M, Sun WNC. Complement pathway inhibitors binding to C5 and. C5a without preventing the formation of C5b. US230522; 2013
135. Fung MSC, Sun C, Sun BNC. Inhibition of complement C5 activation for the treatment and prevention of delayed xenograft or acute vascular rejection. PT1325033; 2010. US041875; 2002
136. Rother RP, Bedrosian C, Squinto SP, Bell L. Methods and compositions for treating complement-Associated disorders. US225056; 2012
137. Magro C. Methods and compositions for treating Degos' disease. US0064820; 2013. MX010116; 2012
138. Berghard C, Berglund M, Stromberg P, et al. Polypeptides binding to human complement C5. WO126006; 2013
139. Francois C, Deschatelets P, Olson P. Modulation and repletion/replacement of the complement system for treatment of trauma. US190221; 2011
140. Nunn MA. Complement inhibitors. US263482; 2011
141. Nunn MA, Lea SM, Roversi P. Modified OMCI as a complement inhibitor. US115773; 2012
142. Hamer J, Weston-Davies W. Method of treating myasthenia gravis. US209459; 2009
143. Hamer J. Method of treating respiratory disorders. US105611; 2010
144. Hamer J. Method of treating peripheral nerve disorders. US111929; 2010
145. Epstein D, Kurz JC. Complement binding aptamers and anti-C5 agents useful in the treatment of ocular disorders. AU204622; 2013. JP067661; 2013
146. Benedict C, Epstein D, Wilson C, et al. Aptamer therapeutics useful in the treatment of complement-related disorders. US0237589; 2013
147. Wang Y. Mutated Fc monoclonal antibodies specific to C5, C5 convertase, C5a or C5b-9 which do not activate complement cascade for use in treatment of pulmonary conditions. NZ563509; 2010. US027160; 2005
148. Tamburini PP. Bispecific antibodies that bind to complement proteins. US002931; 2011
149. Baas F, Fluiter K. Complement antagonists and uses thereof. US171176; 2011
150. Kirsch WM, Crofton A, Freeman T, et al. Substances and methods for the treatment of cerebral amyloid angiopathy related conditions or diseases. WO138368; 2013
151. Smith RJH, Zhang Y, Marsh HC. Treatment of chronic nephropathies using soluble complement receptor type 1 (SCR1). US071413; 2012
152. Seelen MA. Method of improving transplant function using soluble complement receptor type 1 (SCRl). US232020; 2012
153. Lake P, Mullon C. Immunosuppressive combination and its use in the treatment or prophylaxis of insulin-producing cell graft rejection. US236382; 2011
154. Chen X, Holers VM. Three-dimensional structure of complement receptor type 2 and uses thereof. US266571; 2013
155. Kovacs JM, Hannan JP, Holers VM. Complement receptor 2 (CR2) targeting groups. US190477; 2013
156. Tomlinson S, Holers VM. Complement receptor 1 and 2 fusion proteins. US8540997; 2013
157. Robinson WH, Holers VM, Rozelle AL. Complement inhibitory agents as therapeutics in post-Traumatic and degenerative arthritis. US324585; 2009
158. Gilkeson G, Tomlinson S, Holers VM, Rohrer B. Targeting complement factor H for treatment of diseases. US015127; 2011. US221011; 2008
159. Holers VM, Ristano AM. Treatment of paroxysmal nocturnal hemoglobinuria, hemolytic anemias and disease states involving intravascular and extravascular hemolysis. US029912; 2013
160. Würzner R, Lesiak-Markowicz I. CAHGTIP inhibitors for use in the treatment of candidiasis. WO017691; 2013
161. Yang C. Modulation of complement system activation for treatment of bleeding-related inflammation. US092493; 2010
162. Lambris JD, Markiewski MM. Complement inhibitors as therapeutic agents for treatment of cancer. US044983; 2011
163. Lambris JD, Ignatius A, Huber-Lang M. Promotion of fracture healing using complement inhibitors. WO162215; 2012
164. Fan P, Greenman KL, Leleti MR, et al. C5aR antagonists. US0317028; 2013
165. Zipfel P, Skerka C, Wallich R. Novel regulators of the innate immune system. US236455; 2011
166. Atkinson JP, Hourcade D, Krych M. Modified truncated complement system regulators. US119400; 2008
167. Medof EM, Kuttner-Kondo L. Hybrid and chimeric polypeptides that regulate activation of complement. US226020; 2012
168. Garred P, Glue TH, Skjodt MO. Chimeric inhibitor molecules of complement activation. US217616; 2013
169. Baas F, Ramaglia V. Complement inhibition for improved nerve regeneration. US143344; 2010
170. Kumar-Singh R, Cashman SM, Sweigard JH. Compositions, methods and kits for modeling, diagnosing, and treating complement disorders. US149373; 2013
171. Kumar-Singh R, Cashman SM, Ramo K. Compositions, kits and methods for treatment of complement-related disorders. US143953; 2013
172. Li Z, Song S, Xu Z, et al. Fusion protein of antibody targeted complement regulatory factor for treating myasthenia gravis. CN102115499; 2011
173. Song H, Zhang C, Jia L, et al. Novel targeted fusion protein with anti-inflammatory action and use thereof. CN101475644; 2011
174. Song H, Zhang C, Jia L, et al Antibody targeted complement inhibitor with anti-inflammatory action. CN101602809; 2009
175. Gronski P, Licht C, Hoppe B, et al. Factor H for the treatment of chronic nephropathies and production thereof. US046062; 2011
176. Hageman GS. Therapeutic compositions for age-related macular degeneration comprising a complement factor H with isoleucine at residue 62 and tyrosine at residue 402. US8497350; 2013
177. Lambris JD. Factor H binding peptides and uses thereof. WO087925; 2012. EP2655400; 2013
178. Heinen S, Lambris JD, Lauer N, et al. Potent inhibitors of complement activation. WO095519; 2012
179. Lachmann P. Treatment of diseases related to hyperactivity of the complement system. US087905; 2012
180. Chen D, Jin J. Shikonin compound and purpose thereof in preparing anti-Complement medicines. CN103083292; 2013
181. Chen D, Jin J. Boraginaceae phenol compound and purpose thereof in preparing anti-Complement medicines. CN103087020; 2013
182. Chen D, Jin J, Li G. Shikonin tetramer compound and purpose thereof in pharmacy. CN103086864; 2013
183. Chen D, Jin J. Alkannin dimer compounds and uses of the same in drug preparation. CN103086863; 2013
184. Chen D, Jin J. Application of flavan compound in preparing anti-Complement medicines. CN103083342; 2013
185. Sun L, Xi Z, Sun L, et al Acylated flavonoid glycoside compounds and application thereof in preparation of complement inhibitor medicines. CN102304158; 2012
186. Chen D, He C. Application of formononetin in preparation of anti-Complement medicines. CN102100691; 2011
187. Chen D, Fu L, Liu R. Phenolic acid compound and use thereof in the preparation of anti-Complementary medicaments. CN101817746; 2010
188. Allegretti A, Moriconi A, Aramini A, et al. (R)-Arylalkylamino derivatives and pharmaceutical compositions containing them. US124664; 2009
189. Moriconi A, Aramini A. (R)-4-(Heteroaryl) phenylethyl derivatives and pharmaceutical compositions containing them. US249198; 2010
190. Woodruff TM, Taylor SM. Treatment of neurological conditions using complement C5a receptor modulators. US227492; 2009
191. Levdanskij VA, Levdanskij AV, Sokolenko VA, et al. Method of obtaining betulin 3,28-disulfate. RU2468031; 2011
192. Levdanskij VA, Levdanskij AV. Method of obtaining betulin 3,28-disulfate. RU2461561; 2011
193. Levdanskij VA, Levdanskij AV, Kuznetsov BN. Method of producing sodium salt of 3-sulphate betulinic acid. RU2479588; 2012
194. Levdanskij VA, Levdanskij AV. Method for preparing betulinic acid 3-sulphate disodium salt. RU2482123; 2012
195. Larghi EL, Operto MA, Torres R, Kaufman TS. Compuestos inhibidores del complemento, sus sales y derivados farmacéuticamente aceptables, procedimientos para su preparación y composiciones farmacéuticas que los comprenden. AR0101056; 2012
196. Larghi EL, Operto MA, Torres R, Kaufman TS. Synthesis and classical pathway complement inhibitory activity of C7-functionalized filifolinol derivatives, inspired in K-76 COOH. Eur J Med Chem 2012;55:74-84
197. Larghi EL, Operto MA, Torres R, Kaufman TS. New inhibitors of the complement system inspired in K76-COOH. A SAR study of filifolinol derivatives through modifications of the C3' position. Bioorg Med Chem Lett 2009;19:6172-5
198. Useglio M, Castellano PM, Operto MA, et al. Synthesis and complement inhibitory activity of 3H-spiro [benzofuran-2,1'-cyclohexanes] derived from the naturally-occurring filifolinol. Bioorg Med Chem Lett 2006;16:5097-101 (Pubitemid 44255888
199. Bradbury BJ, Bartyzel P, Kaufman TS, et al. Synthesis and complement inhibitory activity of B/C/D/-ring analogues of the fungal metabolite 6,7-diformyl-3',4',4a',5', 6',7',8',8a'-octahydro-4,6',7'-Trihydroxy-2',5',8a'- Tetramethylspiro[1'(2'H)-naphthalene-2(3H)-benzofuran]. J Med Chem 2003;46:2697-705
200. Kaufman TS, Srivastava RP, Sindelar RD, et al. Design, synthesis, and evaluation of A/C/D-ring analogs of the fungal metabolite K-76 as potential complement inhibitors. J Med Chem 1995;38:1437-45
201. Patil G. Hydroxylamine compounds and methods of their use. EP2620429; 2008