USOO8883146 B2 (12) United States Patent (10) Patent No.: US 8,883,146 B2 Fraunhofer et al. (45) Date of Patent: *Nov. 11, 2014 (54) PROTEINFORMULATIONS AND METHODS (56) References Cited OF MAKING SAME U.S. PATENT DOCUMENTS (71) Applicant: AbbVie Inc., North Chicago, IL (US) 4,597,966 A 7/1986 Zolton et al. 4,877,608 A 10, 1989 Lee et al. (72) Inventors: Wolfgang Fraunhofer, Gurnee, IL (US); 5,237,054 A 8, 1993 Brinks et al. Annika Bartl, Ludwigshafen (DE); 5,608,038 A 3, 1997 Eiblet al. Hans-Juergen Krause, Biblis (DE); 5,702,699 A 12/1997 Hanish et al. Markus Tschoepe, Hessheim (DE); 6,090,382 A T/2000 Salfeld et al. Katharina Kaleta, Ludwigshafen (DE) 6,165.467 A 12/2000 Hagiwara et al. 6,171,586 B1 1/2001 Lam et al. 6,252,055 B1 6/2001 Relton (73) Assignee: AbbVie Inc., North Chicago, IL (US) 6,258,562 B1 7/2001 Salfeld et al. 6,281,336 B1 8/2001 Laursen et al. (*) Notice: Subject to any disclaimer, the term of this 6,436,397 B1 8/2002 Baker et al. patent is extended or adjusted under 35 6,485,932 B1 1 1/2002 McIntosh et al. U.S.C. 154(b) by 0 days. 6,509,015 B1 1/2003 Salfeld et al. 6,693,173 B2 2/2004 Mamidi et al. This patent is Subject to a terminal dis- 7,070,775 B2 7/2006 Le et al. claimer. 7,223,394 B2 5/2007 Salfeld et al. 7,250,165 B2 7/2007 Heavner et al. (21) Appl. No.: 13/774,735 7,276,239 B2 10/2007 Le et al. 7,541,031 B2 6/2009 Salfeld et al. (22) Filed: Feb. 22, 2013 7,588,761 B2 9/2009 Salfeld et al. 7,758,860 B2 7/2010 Warne et al. (65) Prior Publication Data 7,863,426 B2 1/2011 Wan et al. 7.919,264 B2 4/2011 Maksymowych et al. US 2013/0156760 A1 Jun. 20, 2013 8,034,906 B2 10/2011 Borhani et al. 8,092,998 B2 1/2012 Stuhlmuller et al. 8,093,045 B2 1 2012 Pla et al. Related U.S. Application Data 8, 187,836 B2 5, 2012 Hsieh (63) Continuation of application No. 12/325,049, filed on 8, 197,813 B2 6/2012 Salfeld et al. Nov. 28, 2008, now Pat. No. 8,420,081. (Continued) (60) Provisional application No. 61/004,992, filed on Nov. FOREIGN PATENT DOCUMENTS 30, 2007. EP 0486526 5, 1992 (51) Int. Cl. EP 419251 B 1, 1993 A 6LX39/395 (2006.01) (Continued) A6 IK39/00 (2006.01) A6 IK38/00 (2006.01) OTHER PUBLICATIONS C07K 16/00 (2006.01) C07K 6/24 (2006.01) Abbott “Humira Prescribing Info..”. Jan. 31, 2003.* CI2P 2/08 (2006.01) A6 IK9/00 (2006.01) (Continued) A6 IK9/08 (2006.01) 3. I 3.08: Primary Examiner — Robert Landsman A6 IK38/46 (2006.01) Assistant Examiner — Bruce D Hissong A6 IK38/48 (2006.01) (74) Attorney, Agent, or Firm — McCarter & English LLP: A6 IK38/50 (2006.01) Cristin H. Cowles; Deborah L. Nagle C07K L/34 (2006.01) (52) U.S. Cl. CPC ........... A61K.39/3955 (2013.01); A61 K9/0019 (57) ABSTRACT (2013.01); A61K 9/08 (2013.01); A61 K9/19 (2013.01); A61 K38/21 (2013.01); A61 K38/46 The invention provides an aqueous formulation comprising (2013.01); A61K 38/4893 (2013.01); A61 K water and a protein, and methods of making the same. The 38/50 (2013.01); A61K.39/395 (2013.01); aqueous formulation of the invention may be a high protein A61K.39/39591 (2013.01); C07K I/34 formulation and/or may have low levels of conductity result (2013.01) ing from the low levels of ionic excipients. Also included in USPC ... 424/130.1; 424/145.1: 514/1.1 : 530/387.1; the invention are formulations comprising water and proteins 530/388.23 having low osmolality. (58) Field of Classification Search None See application file for complete search history. 18 Claims, 36 Drawing Sheets US 8,883,146 B2 Page 2 (56) References Cited 2007/0237762 A1 10, 2007 Winter 2007/0244.299 A1 10, 2007 Jaber U.S. PATENT DOCUMENTS 2007/0253984 A1 11/2007 Khandke et al. 2007/02694.63 A1 11/2007 Donovan et al. 8,206,714 B2 6, 2012 Salfeld et al. 2007,0292442 A1 12/2007 Wan et al. 8,216,583 B2 7/2012 Kruase et al. 2008.0003220 A1 1/2008 Gokarn 8,231,876 B2 7/2012 Wan et al. 2008, 0071063 A1 3, 2008 Alan et al. 8,372.400 B2 2/2013 Salfeld et al. 2008. O112953 A1 5/2008 McAuley et al. 8,372.401 B2 2/2013 Salfeld et al. 2008.0118496 A1 5/2008 Medich et al. 8,414,894 B2 4/2013 Salfeld et al. 2008/O124326 A1 5/2008 Rehder et al. 8.420,081 B2 4/2013 Fraunhofer et al. 2008. O1313.74 A1 6/2008 Medich et al. 8.436,149 B2 5, 2013 Borhani et al. 2008/O139792 A1 6/2008 Seket al. 2003, OO12786 A1 1/2003 Teoh et al. 20080145383 A1 6/2008 Zauner et al. 2003/004.5454 A1 3f2003 Okumu et al. 2008.0161230 A1 7/2008 Jones et al. 2003/0138417 A1 7/2003 Kaisheva et al. 2008/0166348 Al 72008 Kupper et al. 2003/0143603 A1 7/2003 Giles-Komar et al. 2008/0193466 A1 8/2008 Banerjee et al. 2003/0161828 A1 8/2003. Abdelghany et al. 2008, 0200655 A1 8, 2008 Sek 2003/0180287 A1 9, 2003 Gombotz et al. 2008/0227136 Al 9, 2008 Pla et al. 2003/O190316 A1 10, 2003 Kakuta et al. 2008/0275220 A1 11/2008 FrieSS 2003/0206898 A1 11, 2003 Fischkoffetal. 2008/0280345 A1 11/2008 Turner et al. 2003/0219438 A1 11, 2003 Salfeld et al. 2008/0311043 A1 12/2008 Hoffman et al. 2003/0235585 A1 12, 2003 Fischkoffetal. 2008/0311078 A1 12/2008 Gokarn et al. 2004.0009172 A1 1/2004 Fischkoffet al. 2009, OO17472 A1 1/2009 Stuhlmuller et al. 2004/0028667 A1 2/2004 Norman et al. 2009/0028794 A1 1/2009 Medich et al. 2004/0033228 A1 2/2004 Krause et al. 2009.0054331 A1 2/2009 Chen et al. 2004/0038878 A1 2/2004 Tanikawa et al. 2009/006872 A1 3/2009 Kaymakcalan et al. 2004/0105889 A1 6/2004 Ryde et al. 2009/0110679 A1 4, 2009 Li et al. 2004/0126372 A1 7/2004 Banerjee et al. 2009/0123378 A1 5/2009 Wong et al. 2004/0126373 A1 7/2004 Banerjee et al. 2009, O1484.06 A1 6, 2009 Jezek 2004/O131614 A1 7/2004 Banerjee et al. 2009, O1485.13 A1 6/2009 Fraunhofer et al. 2004/O136989 A1 7/2004 Banerjee et al. 2009. O155205 A1 6/2009 Salfeld et al. 2004/O136990 A1 7/2004 Banerjee et al. 2009, 0226530 A1 9, 2009 Lassner et al. 2004/0136991 A1 7/2004 Banerjee et al. 2009/02392.59 Al 9, 2009 Hsieh et al. 2004/0151722 A1 8/2004 Banerjee et al. 2009,0258018 A1 10, 2009 Medich et al. 2004/01661 11 A1 8/2004 Kaymakcalan et al. 2009/0271164 Al 10/2009 Peng et al. 2004/0170623 A1 9, 2004 Arvinte et al. 2009,0280065 A1 11/2009 Willian et al. 2004/019 1243 A1 9/2004 Chen et al. 2009,0291062 A1 11/2009 Fraunhofer et al. 2004/O197324 A1 10, 2004 Liu et al. 2009/0304682 A1 12/2009 Hoffman et al. 2004/0213785 A1 10, 2004 Yamazaki et al. 20090317399 A1 12/2009 Pollack et al. 2004/0219142 A1 1 1/2004 Banerjee et al. 2010.0003243 A1 1/2010 Okun et al. 2004/0228913 A1 11/2004 Kumar et al. 2010, OO16557 A1 1/2010 Salfeld et al. 2005.0053598 A1 3, 2005 Burke et al. 2010/0021451 A1 1/2010 Wong et al. 2005, 0118163 A1 6/2005 Mizushima et al. 2010, 0028372 A1 2/2010 Jezek 2005, 0118167 A1 6, 2005 Okada et al. 2010, 0028383 A1 2/2010 Van Gelder et al. 2005/01 19172 A1 6, 2005 Merkle 2010.0034823 A1 2/2010 Borhani et al. 2005/0214278 A1 9, 2005 Kakuta et al. 2010.0040604 A1 2/2010 Salfeld et al. 2006/0009385 A1 1/2006 Hoffman et al. 2010.0040630 A1 2/2010 Elden et al. 2006, 0083741 A1 4/2006 Hoffman et al. 2010.0113744 A1 5, 2010 Tsvetkova et al. 2006, OO88523 A1 4/2006 Andya et al. 2010/0129379 A1 5/2010 Carpenter et al. 2006, O115472 A1 6, 2006 Li et al. 2010, 0160894 A1 6, 2010 Julian et al. 2006, O142549 A1 6, 2006 Takeda et al. 2010/0278822 A1 11/2010 Fraunhofer et al. 2006/0149042 A1 7/2006 Konstantinov et al. 2011/0014676 A1 1/2011 Cowan et al. 2006/0153846 A1 7/2006 Krause et al. 2011/0054414 A1 3/2011 Shang et al. 2006, O159653 A1 7, 2006 Saito et al. 2011/0171227 A1 7, 2011 Okun et al. 2006, O18274.0 A1 8/2006 Yang et al. 2011/0236391 A1 9, 2011 Mahler et al. 2006/0210557 A1 9, 2006 Luisi et al. 2011/0300151 A1 12/2011 Okun et al. 2006/0246073 Al 1 1/2006 Knight et al. 2012/00 14956 A1 1/2012 Kupper et al. 2006/02694.79 A1 11, 2006 Colton et al. 2012/0077213 A1 3/2012 Pla et al.