IP Library › Granted Patent US 12,521,345
Granted Patent B1
US 12,521,345 · App. 18/825,766 · Granted Jan 13, 2026

Large-scale manufacturing methods for aminoglycosides

Inventor: Robert Worsham (Bridgewater, NJ)
Assignee: Insmed Incorporated
A61K9/1277A61K31/7036
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Quick Facts
Patent No.
US 12,521,345
App. No.
18/825,766
Granted
Jan 13, 2026
Kind
B1
Abstract

Provided herein are large-scale manufacturing methods for drug formulations containing an aminoglycoside such as amikacin. The method utilizes mixing a first stream comprising DPPC and cholesterol with a second stream comprising amikacin sulfate at particular flow rates to obtain a drug formulation with a superior encapsulation efficiency. The processes described herein address the need for preparing aminoglycoside drug formulations at commercial scale.

Claims (21)

1 . A large-scale method of preparing a liposomal amikacin sulfate formulation, wherein the liposomal amikacin sulfate formulation comprises amikacin sulfate encapsulated in a lipid, and liposomes in the liposomal amikacin sulfate formulation have a mean diameter of about 200 nm to about 400 nm, the method comprising:

(a) mixing a first stream comprising an alcoholic solution of the lipid, wherein the lipid consists of dipalmitoyl phosphatidylcholine (DPPC) and cholesterol, with a second stream consisting of an aqueous solution of amikacin sulfate to form a combined lipid-amikacin sulfate stream, wherein the concentration of the lipid in the first stream is from about 10 g/L to about 30 g/L, the concentration of amikacin sulfate in the second stream is from 40 g/L to 45 g/L, and an amount of amikacin sulfate in the second stream is equivalent to about 5 kg to about 50 kg of amikacin,

(b) mixing the lipid-amikacin sulfate stream of Step (a) with an aqueous saline solution in a reaction vessel, wherein the aqueous saline solution consists of water and sodium chloride, and

(c) washing the product of Step (b) comprising the liposomal amikacin sulfate formulation to remove unencapsulated amikacin sulfate and to provide a washed liposomal amikacin sulfate formulation having an overall ratio of the weight of the lipid to the equivalent weight of amikacin of between about 0.5 (lipid): 1 (amikacin) and about 0.8 (lipid): 1 (amikacin),

wherein the relative flow rate ratio of the second stream to the first stream is about 1.5:1 to about 2:1.

2 . The method of claim 1 , wherein the aqueous saline solution is added to the reaction vessel via a third stream.

3 . The method of claim 1 , wherein the flow rate of the first stream is from about 0.5 kg/min to about 1.5 kg/min, and the flow rate of the second stream is from about 1 kg/min to about 2 kg/min.

4 . The method of claim 1 , wherein the flow rate of the first stream is from about 3 kg/min to about 4 kg/min, and the flow rate of the second stream is from about 5 kg/min to about 7 kg/min.

5 . The method of claim 1 , wherein the aqueous saline solution consists of about 0.5-2% aqueous sodium chloride solution.

6 . The method of claim 1 , wherein the second stream comprising amikacin sulfate and the first stream comprising the lipid are each maintained at a temperature from about 30° C. to about 50° C. prior to mixing.

7 . The method of claim 1 , wherein following Step (b) the liposomes are prepared with an amikacin sulfate encapsulation efficiency of at least 40%.

8 . The method of claim 1 , wherein the washing Step (c) is performed using 1.5% aqueous sodium chloride solution.

9 . The method of claim 8 , wherein the washing Step (c) is repeated, and the product concentrated to provide the liposomal amikacin sulfate formulation with amikacin sulfate present at a concentration of from about 60 g/L to about 80 g/L.

10 . The method of claim 1 , wherein the concentration of the lipid in the first stream is about 20 g/L.

11 . The method of claim 1 , wherein the concentration of amikacin sulfate in the second stream is 45 g/L.

12 . The method of claim 1 , wherein the washed liposomal amikacin sulfate formulation has an overall ratio of the weight of the lipid to the equivalent weight of amikacin of between about 0.5 (lipid):1 (amikacin) and about 0.6 (lipid):1 (amikacin).

13 . The method of claim 1 , wherein the washed liposomal amikacin sulfate formulation has an overall ratio of the weight of the lipid to the equivalent weight of amikacin of about 0.7 (lipid):1 (amikacin).

14 . The method of claim 2 , wherein the third stream is added to the reaction vessel at the same time as the lipid-amikacin sulfate stream.

15 . The method of claim 5 , wherein the aqueous saline solution consists of about 1.5% aqueous sodium chloride solution.

16 . The method of claim 9 , wherein amikacin sulfate is present at a concentration of about 70 g/L in the liposomal amikacin sulfate formulation.

17 . The method of claim 9 , wherein the lipid is present at a concentration from about 40 g/L to about 60 g/L in the liposomal amikacin sulfate formulation.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 26, 2024
From: WORSHAM, ROBERT
To: INSMED INCORPORATED
Reel/Frame 069032/0291 →
Continuity (2)
Continuation 17052070
Provisional Application 62665564 · May 2, 2018
References Cited (400)
US 3091572A · Luedemann et al. · 1963 [cited by applicant]
US 3136704A · William et al. · 1964 [cited by applicant]
US 4235871A · Papahadjopoulos et al. · 1980 [cited by applicant]
US 4372949A · Kodama et al. · 1983 [cited by applicant]
US 4394448A · Szoka, Jr. et al. · 1983 [cited by applicant]
US 4396630A · Riedl et al. · 1983 [cited by applicant]
US 4451447A · Kaplan et al. · 1984 [cited by applicant]
US 4515736A · Deamer · 1985 [cited by applicant]
US 4522803A · Lenk et al. · 1985 [cited by applicant]
US 4547490A · Ecanow et al. · 1985 [cited by applicant]
US 4588578A · Fountain et al. · 1986 [cited by applicant]
US 4606939A · Frank et al. · 1986 [cited by applicant]
US 4684625A · Eppstein et al. · 1987 [cited by applicant]
US 4693999A · Axelsson et al. · 1987 [cited by applicant]
US 4721612A · Janoff et al. · 1988 [cited by applicant]
US 4767874A · Shima et al. · 1988 [cited by applicant]
US 4833134A · Kishimoto et al. · 1989 [cited by applicant]
US 4857311A · Domb et al. · 1989 [cited by applicant]
US 4895452A · Yiournas et al. · 1990 [cited by applicant]
US 4895719A · Radhakrishnan et al. · 1990 [cited by applicant]
US 4897384A · Janoff et al. · 1990 [cited by applicant]
US 4933121A · Law et al. · 1990 [cited by applicant]
US 4952405A · Yau-Young · 1990 [cited by applicant]
US 4963367A · Ecanow · 1990 [cited by applicant]
US 4975282A · Cullis et al. · 1990 [cited by applicant]
US 4981692A · Popescu et al. · 1991 [cited by applicant]
US 5000958A · Fountain et al. · 1991 [cited by applicant]
US 5006343A · Benson et al. · 1991 [cited by applicant]
US 5008050A · Cullis et al. · 1991 [cited by applicant]
US 5023087A · Yau-Young · 1991 [cited by applicant]
US 5030453A · Lenk et al. · 1991 [cited by applicant]
US 5041278A · Janoff et al. · 1991 [cited by applicant]
US 5049388A · Knight et al. · 1991 [cited by applicant]
US 5049389A · Radhakrishnan · 1991 [cited by applicant]
US 5059421A · Loughrey et al. · 1991 [cited by applicant]
US 5059591A · Janoff et al. · 1991 [cited by applicant]
US 5077056A · Bally et al. · 1991 [cited by applicant]
US 5169637A · Lenk et al. · 1992 [cited by applicant]
US 5178876A · Khokhar et al. · 1993 [cited by applicant]
US 5192549A · Barenolz et al. · 1993 [cited by applicant]
US 5211955A · Legros et al. · 1993 [cited by applicant]
US 5252339A · Cristofori et al. · 1993 [cited by applicant]
US 5264618A · Felgner et al. · 1993 [cited by applicant]
US 5269979A · Fountain · 1993 [cited by applicant]
US 5279833A · Rose · 1994 [cited by applicant]
US 5316771A · Barenholz et al. · 1994 [cited by applicant]
US 5320906A · Eley et al. · 1994 [cited by applicant]
US 5334761A · Gebeyehu et al. · 1994 [cited by applicant]
US 5401511A · Margalit · 1995 [cited by applicant]
US 5409704A · Bally et al. · 1995 [cited by applicant]
US 5415867A · Minchey et al. · 1995 [cited by applicant]
US 5459127A · Felgner et al. · 1995 [cited by applicant]
US 5508269A · Smith et al. · 1996 [cited by applicant]
US 5540936A · Coe et al. · 1996 [cited by applicant]
US 5543152A · Webb et al. · 1996 [cited by applicant]
US 5549102A · Lintl et al. · 1996 [cited by applicant]
US 5569464A · Endo et al. · 1996 [cited by applicant]
US 5578320A · Janoff et al. · 1996 [cited by applicant]
US 5580575A · Unger et al. · 1996 [cited by applicant]
US 5596982A · Blaha-Schnabel · 1997 [cited by applicant]
US 5610198A · Barry, III et al. · 1997 [cited by applicant]
US 5614216A · Janoff · 1997 [cited by applicant]
US 5616334A · Janoff et al. · 1997 [cited by applicant]
US 5616341A · Mayer et al. · 1997 [cited by applicant]
US 5631018A · Zalipsky et al. · 1997 [cited by applicant]
US 5641662A · Debs et al. · 1997 [cited by applicant]
US 5643599A · Lee et al. · 1997 [cited by applicant]
US 5662929A · Lagace et al. · 1997 [cited by applicant]
US 5665383A · Grinstaff et al. · 1997 [cited by applicant]
US 5723147A · Kim et al. · 1998 [cited by applicant]
US 5736155A · Bally et al. · 1998 [cited by applicant]
US 5740966A · Blaha-Schnabel · 1998 [cited by applicant]
US 5741516A · Webb et al. · 1998 [cited by applicant]
US 5753613A · Ansell et al. · 1998 [cited by applicant]
US 5756120A · Hersch et al. · 1998 [cited by applicant]
US 5756121A · Bracken · 1998 [cited by applicant]
US 5756353A · Debs · 1998 [cited by applicant]
US 5759571A · Hersch et al. · 1998 [cited by applicant]
US 5766627A · Sankaram et al. · 1998 [cited by applicant]
US 5785987A · Hope et al. · 1998 [cited by applicant]
US 5795589A · Mayer et al. · 1998 [cited by applicant]
US 5814335A · Webb et al. · 1998 [cited by applicant]
US 5820848A · Boni et al. · 1998 [cited by applicant]
US 5823178A · Lloyd et al. · 1998 [cited by applicant]
US 5837279A · Janoff et al. · 1998 [cited by applicant]
US 5837282A · Fenske et al. · 1998 [cited by applicant]
US 5840702A · Bedwell · 1998 [cited by applicant]
US 5843473A · Woodle et al. · 1998 [cited by applicant]
US 5849490A · Schonwetter et al. · 1998 [cited by applicant]
US 5861159A · Pardoll et al. · 1999 [cited by applicant]
US 5871710A · Bogdanov et al. · 1999 [cited by applicant]
US 5875776A · Vaghefi · 1999 [cited by applicant]
US 5883074A · Boggs et al. · 1999 [cited by applicant]
US 5891468A · Martin et al. · 1999 [cited by applicant]
US 5922350A · Janoff et al. · 1999 [cited by applicant]
US 5939096A · Clerc et al. · 1999 [cited by applicant]
US 5945122A · Abra et al. · 1999 [cited by applicant]
US 5957389A · Wunderlich et al. · 1999 [cited by applicant]
US 5958449A · Hersch et al. · 1999 [cited by applicant]
US 5965549A · Purwar et al. · 1999 [cited by applicant]
US 5972379A · Guo et al. · 1999 [cited by applicant]
US 5993850A · Sankaram et al. · 1999 [cited by applicant]
US 6000394A · Blaha-Schnabel et al. · 1999 [cited by applicant]
US 6045828A · Bystrom et al. · 2000 [cited by applicant]
US 6051251A · Zalipsky et al. · 2000 [cited by applicant]
US 6051549A · Roberts et al. · 2000 [cited by applicant]
US 6083530A · Mayer et al. · 2000 [cited by applicant]
US 6085741A · Becker · 2000 [cited by applicant]
US 6086851A · Boni et al. · 2000 [cited by applicant]
US 6090407A · Knight et al. · 2000 [cited by applicant]
US 6093730A · Weidmann et al. · 2000 [cited by applicant]
US 6106479A · Wunderlich et al. · 2000 [cited by applicant]
US 6106858A · Ye et al. · 2000 [cited by applicant]
US 6124273A · Drohan et al. · 2000 [cited by applicant]
US 6147060A · Zasloff et al. · 2000 [cited by applicant]
US 6162462A · Bolotin et al. · 2000 [cited by applicant]
US 6176237B1 · Wunderlich et al. · 2001 [cited by applicant]
US 6197333B1 · Onyuksel et al. · 2001 [cited by applicant]
US 6211162B1 · Dale et al. · 2001 [cited by applicant]
US 6221385B1 · Camu et al. · 2001 [cited by applicant]
US 6221388B1 · Hersch et al. · 2001 [cited by applicant]
US 6228346B1 · Zhang et al. · 2001 [cited by applicant]
US 6228393B1 · DiCosmo et al. · 2001 [cited by applicant]
US 6235177B1 · Borland et al. · 2001 [cited by applicant]
US 6274175B1 · Gombotz et al. · 2001 [cited by applicant]
US 6316024B1 · Allen et al. · 2001 [cited by applicant]
US 6338859B1 · Leroux et al. · 2002 [cited by applicant]
US 6348069B1 · Vacanti et al. · 2002 [cited by applicant]
US 6352996B1 · Cao et al. · 2002 [cited by applicant]
US 6355267B1 · Collins · 2002 [cited by applicant]
US 6387886B1 · Montgomery et al. · 2002 [cited by applicant]
US 6419901B2 · Placke et al. · 2002 [cited by applicant]
US 6440393B1 · Waldrep et al. · 2002 [cited by applicant]
US 6443898B1 · Unger et al. · 2002 [cited by applicant]
US 6447753B2 · Edwards et al. · 2002 [cited by applicant]
US 6451784B1 · Placke et al. · 2002 [cited by applicant]
US 6458373B1 · Lambert et al. · 2002 [cited by applicant]
US 6468532B1 · Hsei et al. · 2002 [cited by applicant]
US 6475779B2 · Mathiowitz et al. · 2002 [cited by applicant]
US 6481438B1 · Gallem et al. · 2002 [cited by applicant]
US 6492560B2 · Wilbur et al. · 2002 [cited by applicant]
US 6497901B1 · Royer · 2002 [cited by applicant]
US 6509323B1 · Davis et al. · 2003 [cited by applicant]
US 6511676B1 · Boulikas · 2003 [cited by applicant]
US 6513727B1 · Jaser et al. · 2003 [cited by applicant]
US 6518243B1 · Kahne et al. · 2003 [cited by applicant]
US 6521211B1 · Unger et al. · 2003 [cited by applicant]
US 6521736B2 · Watterson et al. · 2003 [cited by applicant]
US 6534018B1 · Baker et al. · 2003 [cited by applicant]
US 6546927B2 · Litherland et al. · 2003 [cited by applicant]
US 6554201B2 · Klimowicz et al. · 2003 [cited by applicant]
US 6596305B1 · Edgerly-Plug · 2003 [cited by applicant]
US 6599912B1 · Au et al. · 2003 [cited by applicant]
US 6606990B2 · Stapleton et al. · 2003 [cited by applicant]
US 6613352B2 · Lagace et al. · 2003 [cited by applicant]
US 6615824B2 · Power · 2003 [cited by applicant]
US 6623671B2 · Coe et al. · 2003 [cited by applicant]
US 6629646B1 · Ivri · 2003 [cited by applicant]
US 6676034B2 · Tanaka et al. · 2004 [cited by applicant]
US 6679251B1 · Gallem et al. · 2004 [cited by applicant]
US 6759057B1 · Weiner et al. · 2004 [cited by applicant]
US 6770291B2 · Smyth-Templeton et al. · 2004 [cited by applicant]
US 6843942B2 · Katinger et al. · 2005 [cited by applicant]
US 6845770B2 · Klimowicz et al. · 2005 [cited by applicant]
US 6855296B1 · Baker et al. · 2005 [cited by applicant]
US 6890555B1 · Desai et al. · 2005 [cited by applicant]
US 6900184B2 · Cohen et al. · 2005 [cited by applicant]
US 6915962B2 · Power et al. · 2005 [cited by applicant]
US 6916490B1 · Garver et al. · 2005 [cited by applicant]
US 6948491B2 · Loeffler et al. · 2005 [cited by applicant]
US 6962151B1 · Knoch et al. · 2005 [cited by applicant]
US 6983747B2 · Gallem et al. · 2006 [cited by applicant]
US 6991809B2 · Anderson · 2006 [cited by applicant]
US 7059320B2 · Feiner et al. · 2006 [cited by applicant]
US 7063860B2 · Chancellor et al. · 2006 [cited by applicant]
US 7077126B2 · Kummer et al. · 2006 [cited by applicant]
US 7100600B2 · Loeffler et al. · 2006 [cited by applicant]
US 7104463B2 · Litherland et al. · 2006 [cited by applicant]
US 7131440B2 · Sonntag · 2006 [cited by applicant]
US 7244413B2 · Barbera-Guillem · 2007 [cited by applicant]
US 7252085B2 · Kunschir · 2007 [cited by applicant]
US 7255106B2 · Gallem et al. · 2007 [cited by applicant]
US 7297344B1 · Fleischer et al. · 2007 [cited by applicant]
US 7331339B2 · Smith et al. · 2008 [cited by applicant]
US 7368102B2 · Tarara et al. · 2008 [cited by applicant]
US D583928S · Knoch · 2008 [cited by applicant]
US 7458372B2 · Feiner et al. · 2008 [cited by applicant]
US 7472701B2 · Pfichner et al. · 2009 [cited by applicant]
US 7544369B2 · Boni et al. · 2009 [cited by applicant]
US 7600511B2 · Power et al. · 2009 [cited by applicant]
US 7686014B2 · Boehm et al. · 2010 [cited by applicant]
US 7718189B2 · Boni et al. · 2010 [cited by applicant]
US 7748377B2 · Smith et al. · 2010 [cited by applicant]
US 7758886B2 · Jauernig et al. · 2010 [cited by applicant]
US 7771642B2 · Power et al. · 2010 [cited by applicant]
US 7779838B2 · Hetzer et al. · 2010 [cited by applicant]
US 7879351B2 · Li et al. · 2011 [cited by applicant]
US 7891352B2 · Gallem et al. · 2011 [cited by applicant]
US 7931212B2 · Urich et al. · 2011 [cited by applicant]
US D638117S · Eckstein et al. · 2011 [cited by applicant]
US 7958887B2 · Kelliher et al. · 2011 [cited by applicant]
US 7971588B2 · Fink et al. · 2011 [cited by applicant]
US 7980247B2 · Boehm et al. · 2011 [cited by applicant]
US 8006698B2 · Boehm et al. · 2011 [cited by applicant]
US 8071127B2 · Cipolla et al. · 2011 [cited by applicant]
US D652908S · Eckstein et al. · 2012 [cited by applicant]
US 8100162B2 · Joern et al. · 2012 [cited by applicant]
US 8113194B2 · Boehm et al. · 2012 [cited by applicant]
US 8119156B2 · Cipolla et al. · 2012 [cited by applicant]
US D656604S · Eckstein et al. · 2012 [cited by applicant]
US 8226975B2 · Weers · 2012 [cited by applicant]
US 8263645B2 · Keller · 2012 [cited by applicant]
US 8268347B1 · Cipolla et al. · 2012 [cited by applicant]
US 8333187B2 · Gallem et al. · 2012 [cited by applicant]
US 8342171B2 · Boehm et al. · 2013 [cited by applicant]
US 8347878B2 · Schuschnig et al. · 2013 [cited by applicant]
US 8387895B2 · Stangl · 2013 [cited by applicant]
US 8398001B2 · Borland et al. · 2013 [cited by applicant]
US D680214S · Eckstein et al. · 2013 [cited by applicant]
US 8414915B2 · Cipolla et al. · 2013 [cited by applicant]
US 8459252B2 · Gallem et al. · 2013 [cited by applicant]
US 8511581B2 · Urich et al. · 2013 [cited by applicant]
US 8596264B2 · Sommer · 2013 [cited by applicant]
US 8616195B2 · Power et al. · 2013 [cited by applicant]
US 8632804B2 · Weers · 2014 [cited by applicant]
US 8642075B2 · Weers · 2014 [cited by applicant]
US 8671933B2 · Boehm et al. · 2014 [cited by applicant]
US 8673348B2 · Weers · 2014 [cited by applicant]
US 8673349B2 · Weers · 2014 [cited by applicant]
US 8679532B2 · Weers · 2014 [cited by applicant]
US 8720432B2 · Borgschulte et al. · 2014 [cited by applicant]
US 8720435B2 · Gallem et al. · 2014 [cited by applicant]
US 8739777B2 · Kreutzmann et al. · 2014 [cited by applicant]
US 8802137B2 · Boni et al. · 2014 [cited by applicant]
US 8852557B2 · Keller et al. · 2014 [cited by applicant]
US 8985100B2 · Minocchieri et al. · 2015 [cited by applicant]
US 9016272B2 · Gallem et al. · 2015 [cited by applicant]
US 9027548B2 · Borgschulte et al. · 2015 [cited by applicant]
US 9028864B2 · Cipolla et al. · 2015 [cited by applicant]
US 9046092B2 · Boehm et al. · 2015 [cited by applicant]
US 9061303B2 · Waldner et al. · 2015 [cited by applicant]
US 9072464B2 · Haartsen et al. · 2015 [cited by applicant]
US 9078897B1 · Cipolla et al. · 2015 [cited by applicant]
US 9084862B2 · Blakey et al. · 2015 [cited by applicant]
US 9095676B2 · Gallem et al. · 2015 [cited by applicant]
US 9108211B2 · Ivri · 2015 [cited by applicant]
US 9114081B2 · Gupta · 2015 [cited by applicant]
US 9119783B2 · Gupta · 2015 [cited by applicant]
US 9119930B2 · Kreutzmann et al. · 2015 [cited by applicant]
US 9149588B2 · Gordon et al. · 2015 [cited by applicant]
US 9161963B2 · Keller et al. · 2015 [cited by applicant]
US 9168556B2 · Pumm et al. · 2015 [cited by applicant]
US 9198859B2 · Keller et al. · 2015 [cited by applicant]
US 9259424B2 · Cipolla et al. · 2016 [cited by applicant]
US 9265900B2 · Loenner et al. · 2016 [cited by applicant]
US 9333214B2 · Gupta · 2016 [cited by applicant]
US 9402845B2 · Weers · 2016 [cited by applicant]
US 9511082B2 · Weers · 2016 [cited by applicant]
US 9549925B2 · Weers · 2017 [cited by applicant]
US 9549939B2 · Weers · 2017 [cited by applicant]
US 9566234B2 · Perkins et al. · 2017 [cited by applicant]
US 9724301B2 · Gupta · 2017 [cited by applicant]
US 9737555B2 · Gupta · 2017 [cited by applicant]
US 9827317B2 · Boni et al. · 2017 [cited by applicant]
US 9895385B2 · Eagle et al. · 2018 [cited by applicant]
US 9925205B2 · Malinin · 2018 [cited by applicant]
US 10064882B2 · Gupta · 2018 [cited by applicant]
US 10124066B2 · Perkins et al. · 2018 [cited by applicant]
US 10238675B2 · Eagle et al. · 2019 [cited by applicant]
US 10251900B2 · Eagle et al. · 2019 [cited by applicant]
US 10328071B2 · Weers · 2019 [cited by applicant]
US 10398719B2 · Eagle et al. · 2019 [cited by applicant]
US 10471149B2 · Perkins et al. · 2019 [cited by applicant]
US 10588918B2 · Eagle et al. · 2020 [cited by applicant]
US 10751355B2 · Eagle et al. · 2020 [cited by applicant]
US 10828314B2 · Eagle et al. · 2020 [cited by applicant]
US 11395830B2 · Eagle et al. · 2022 [cited by applicant]
US 11446318B2 · Eagle et al. · 2022 [cited by applicant]
US 11571386B2 · Worsham · 2023 [cited by applicant]
US 12016873B2 · Eagle et al. · 2024 [cited by applicant]
US 12168021B2 · Eagle et al. · 2024 [cited by applicant]
US 12168022B2 · Eagle et al. · 2024 [cited by applicant]
US 12290600B2 · Worsham · 2025 [cited by applicant]
US 20010006660A1 · Lagace et al. · 2001 [cited by applicant]
US 20020035061A1 · Krieger et al. · 2002 [cited by applicant]
US 20020039596A1 · Hartounian et al. · 2002 [cited by applicant]
US 20020052390A1 · Ponikau · 2002 [cited by applicant]
US 20020086852A1 · Cantor et al. · 2002 [cited by applicant]
US 20020187105A1 · Zou et al. · 2002 [cited by applicant]
US 20030039615A1 · Katz · 2003 [cited by applicant]
US 20030059375A1 · Perez-Soler et al. · 2003 [cited by applicant]
US 20030096774A1 · Gonda et al. · 2003 [cited by applicant]
US 20030099697A1 · Panzner et al. · 2003 [cited by applicant]
US 20030118636A1 · Friesen et al. · 2003 [cited by applicant]
US 20030138481A1 · Zadi · 2003 [cited by applicant]
US 20030148964A1 · Dunne · 2003 [cited by applicant]
US 20030224039A1 · Boni et al. · 2003 [cited by applicant]
US 20040009126A1 · Pilkiewicz et al. · 2004 [cited by applicant]
US 20040032037A1 · Katinger et al. · 2004 [cited by applicant]
US 20040089295A1 · Gallem et al. · 2004 [cited by applicant]
US 20040091541A1 · Unger · 2004 [cited by applicant]
US 20040101553A1 · Lee et al. · 2004 [cited by applicant]
US 20040142025A1 · MacLachlan et al. · 2004 [cited by applicant]
US 20040142026A1 · Boni et al. · 2004 [cited by applicant]
US 20040156888A1 · Jensen et al. · 2004 [cited by applicant]
US 20040180082A1 · Kang et al. · 2004 [cited by applicant]
US 20050019926A1 · Gonda et al. · 2005 [cited by applicant]
US 20050025822A1 · Wong et al. · 2005 [cited by applicant]
US 20050042341A1 · Thomas et al. · 2005 [cited by applicant]
US 20050113337A1 · Taneja et al. · 2005 [cited by applicant]
US 20050119202A1 · Kreutzer et al. · 2005 [cited by applicant]
US 20050207987A1 · Speirs et al. · 2005 [cited by applicant]
US 20050214224A1 · Weers et al. · 2005 [cited by applicant]
US 20050217666A1 · Fink et al. · 2005 [cited by applicant]
US 20050220752A1 · Charmot et al. · 2005 [cited by applicant]
US 20050249795A1 · Zhang et al. · 2005 [cited by applicant]
US 20060062738A1 · Hofmann et al. · 2006 [cited by applicant]
US 20060067998A1 · Kurzrock et al. · 2006 [cited by applicant]
US 20060073198A1 · Boni et al. · 2006 [cited by applicant]
US 20060110441A1 · Wong et al. · 2006 [cited by applicant]
US 20060198940A1 · McMorrow · 2006 [cited by applicant]
US 20060217603A1 · Nagai et al. · 2006 [cited by applicant]
US 20060286038A1 · Rairkar et al. · 2006 [cited by applicant]
US 20070065367A1 · Condos et al. · 2007 [cited by applicant]
US 20070077290A1 · Li et al. · 2007 [cited by applicant]
US 20070081963A1 · Oh et al. · 2007 [cited by applicant]
US 20070105758A1 · May et al. · 2007 [cited by applicant]
US 20070196461A1 · Weers · 2007 [cited by applicant]
US 20070267010A1 · Fink et al. · 2007 [cited by applicant]
US 20080089927A1 · Malinin · 2008 [cited by examiner]
US 20080108104A1 · Eckstein et al. · 2008 [cited by applicant]
US 20080131497A1 · Perkins et al. · 2008 [cited by applicant]
US 20080246472A1 · Igney et al. · 2008 [cited by applicant]
US 20090053489A1 · Yamamura et al. · 2009 [cited by applicant]
US 20090104256A1 · Gupta · 2009 [cited by applicant]
US 20090104257A1 · Li et al. · 2009 [cited by applicant]
US 20090105126A1 · Li et al. · 2009 [cited by applicant]
US 20090269396A1 · Cipolla et al. · 2009 [cited by applicant]
US 20090274754A1 · Cipolla et al. · 2009 [cited by applicant]
US 20100068257A1 · Boni et al. · 2010 [cited by applicant]
US 20100196455A1 · Malinin · 2010 [cited by applicant]
US 20100260829A1 · Boni et al. · 2010 [cited by applicant]
US 20110064796A1 · Cipolla et al. · 2011 [cited by applicant]
US 20110150983A1 · Cipolla et al. · 2011 [cited by applicant]
US 20110159079A1 · Li et al. · 2011 [cited by applicant]
US 20110256175A1 · Hope et al. · 2011 [cited by applicant]
US 20120010162A1 · Norling · 2012 [cited by applicant]
US 20120077786A1 · Byron et al. · 2012 [cited by applicant]
US 20120192861A1 · Surber · 2012 [cited by applicant]
US 20120244206A1 · Cipolla et al. · 2012 [cited by applicant]
US 20130028960A1 · Weers · 2013 [cited by applicant]
US 20130034534A1 · Kroneberg et al. · 2013 [cited by applicant]
US 20130052260A1 · Weers · 2013 [cited by applicant]
US 20130064883A1 · Weers · 2013 [cited by applicant]
US 20130071468A1 · Weers · 2013 [cited by applicant]
US 20130071469A1 · Weers · 2013 [cited by applicant]
US 20130087480A1 · Stark et al. · 2013 [cited by applicant]
US 20130089598A1 · Gupta · 2013 [cited by applicant]
US 20130121918A1 · Hong et al. · 2013 [cited by applicant]
US 20130136788A1 · Gupta · 2013 [cited by applicant]
US 20130177629A1 · Martin et al. · 2013 [cited by applicant]
US 20130280174A1 · Lipic et al. · 2013 [cited by applicant]
US 20130330400A1 · Perkins et al. · 2013 [cited by applicant]
US 20130330440A1 · Fulgham · 2013 [cited by applicant]
US 20140018431A1 · Wade et al. · 2014 [cited by applicant]
US 20140072620A1 · Weers · 2014 [cited by applicant]
US 20140248335A1 · Malinin · 2014 [cited by applicant]
US 20140308304A1 · Manoharan et al. · 2014 [cited by applicant]
US 20140314835A1 · Boni et al. · 2014 [cited by applicant]
US 20140348900A1 · Zhu · 2014 [cited by examiner]
US 20140371293A1 · Brown et al. · 2014 [cited by applicant]
US 20150110855A1 · Cipolla et al. · 2015 [cited by applicant]
US 20150272880A1 · Seidel et al. · 2015 [cited by applicant]
US 20150283076A1 · Cipolla et al. · 2015 [cited by applicant]
US 20150283133A1 · Gonda et al. · 2015 [cited by applicant]
US 20150306173A1 · Chen et al. · 2015 [cited by applicant]
US 20150314002A1 · Perkins et al. · 2015 [cited by applicant]
US 20150328244A1 · Eagle et al. · 2015 [cited by applicant]
US 20160113927A1 · Weers · 2016 [cited by applicant]
US 20160120806A1 · Cipolla et al. · 2016 [cited by applicant]
US 20160143849A1 · Gupta · 2016 [cited by applicant]
US 20160151402A1 · Gupta · 2016 [cited by applicant]
US 20160184301A1 · Weers · 2016 [cited by applicant]
US 20160184302A1 · Weers · 2016 [cited by applicant]
US 20160271125A1 · Boni et al. · 2016 [cited by applicant]
US 20160317563A1 · Weers · 2016 [cited by applicant]
US 20160317564A1 · Weers · 2016 [cited by applicant]
US 20160354371A1 · Weers · 2016 [cited by applicant]
US 20170014342A1 · Li et al. · 2017 [cited by applicant]
US 20170087155A1 · Weers · 2017 [cited by applicant]
US 20170100420A1 · Boni et al. · 2017 [cited by applicant]
US 20170165374A1 · Perkins et al. · 2017 [cited by applicant]
US 20170196900A1 · Perkins et al. · 2017 [cited by applicant]
US 20170225123A1 · Ayturk et al. · 2017 [cited by applicant]
US 20170360816A1 · Eagle et al. · 2017 [cited by applicant]
US 20170360818A1 · Gupta · 2017 [cited by applicant]
US 20180104345A1 · Boni et al. · 2018 [cited by applicant]
US 20180153918A1 · Weers · 2018 [cited by applicant]
US 20180169124A1 · Boni et al. · 2018 [cited by applicant]
US 20180169125A1 · Malinin · 2018 [cited by applicant]