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`Int. Cl. Int. Cl.
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`A 61K 39/395 (cid:9)A 61K 39/395 (cid:9)
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`A 61K 9/00 (cid:9)A 61K 9/00 (cid:9)
`
`C07K 16/24 (cid:9)C07K 16/24 (cid:9)
`
`A61K 39/00 (cid:9)A61K 39/00 (cid:9)
`
`(52) U.S. Cl. (52) U.S. Cl.
`
`CPC CPC
`
`
`(2006.01) (2006.01)
`
`(2006.01) (2006.01)
`
`(2006.01) (2006.01)
`
`(2006.01) (2006.01)
`
`
`A 61K 9/0019 (2013.01); C07K 16/241 A 61K 9/0019 (2013.01); C07K 16/241
`
`(2013.01); A61K 39/3955 (2013.01); A61K (2013.01); A61K 39/3955 (2013.01); A61K
`
`2039/54 (2013.01) 2039/54 (2013.01)
`
` 424/145.1 424/145.1
`
`
`USPC (cid:9)USPC (cid:9)
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`(58) Field of Classification Search (58) Field of Classification Search
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`None None
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`See application file for complete search history. See application file for complete search history.
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`
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`11111111111111111111111114911J1111)1111111111 111111 11110111111 11111111111111111111111114911J1111)1111111111 111111 11110111111
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`US 8,911,737 B2 US 8,911,737 B2
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`Dec. 16, 2014 Dec. 16, 2014
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`
`(54) METHODS OF ADMINISTERING ANTI-TNFa (54) METHODS OF ADMINISTERING ANTI-TNFa
`
`ANTIBODIES ANTIBODIES
`
`
`(71) Applicant: AbbVie Biotechnology Ltd., Hamilton (71) Applicant: AbbVie Biotechnology Ltd., Hamilton
`
`(BM) (BM)
`
`
`
`(72) (72)
`
`
`Inventors: Steven A. Fischkoff, Short Hills, NJ Inventors: Steven A. Fischkoff, Short Hills, NJ
`
`(US); Joachim Kempeni, Neustadt (US); Joachim Kempeni, Neustadt
`
`(DE); Roberta Weiss, Wynnewood, PA (DE); Roberta Weiss, Wynnewood, PA
`
`(US) (US)
`
`
`(73) Assignee: AbbVie Biotechnology Ltd., Hamilton (73) Assignee: AbbVie Biotechnology Ltd., Hamilton
`
`(BM) (BM)
`
`
`
`( * ) Notice: (cid:9)( * ) Notice: (cid:9)
`
`
`Subject to any disclaimer, the term of this Subject to any disclaimer, the term of this
`
`patent is extended or adjusted under 35 patent is extended or adjusted under 35
`
`U.S.C. 154(b) by 0 days. U.S.C. 154(b) by 0 days.
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`
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`Apr. 18, 2014 Apr. 18, 2014
`
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`
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`US 2014/0271637 Al (cid:9)US 2014/0271637 Al (cid:9)
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`
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`Sep. 18, 2014 Sep. 18, 2014
`
`
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`
`
`(Continued) (Continued)
`
`
`Primary Examiner — Zachary Skelding Primary Examiner — Zachary Skelding
`
`(74) Attorney, Agent, or Firm — Dechert LLP (74) Attorney, Agent, or Firm — Dechert LLP
`
`
`
`(57) (cid:9)(57) (cid:9)
`ABSTRACT ABSTRACT
`
`Methods of treating disorders in which TNFa activity is Methods of treating disorders in which TNFa activity is
`
`detrimental via biweekly, subcutaneous administration of detrimental via biweekly, subcutaneous administration of
`
`human antibodies, preferably recombinant human antibod-human antibodies, preferably recombinant human antibod-
`
`ies, that specifically bind to human tumor necrosis factor a ies, that specifically bind to human tumor necrosis factor a
`
`(hTNFa) are disclosed. The antibody may be administered (hTNFa) are disclosed. The antibody may be administered
`
`with or without methotrexate. These antibodies have high with or without methotrexate. These antibodies have high
`
`affinity for hTNFa (e.g., Kd=10-8 M or less), a slow off rate affinity for hTNFa (e.g., Kd=10-8 M or less), a slow off rate
`
`for hTNFa dissociation (e.g., Koc10-3 sec-' or less) and for hTNFa dissociation (e.g., Koc10-3 sec-' or less) and
`
`neutralize hTNFa activity in vitro and in vivo. An antibody of neutralize hTNFa activity in vitro and in vivo. An antibody of
`
`the invention can be a full-length antibody or an antigen-the invention can be a full-length antibody or an antigen-
`
`binding portion thereof Kits containing a pharmaceutical binding portion thereof Kits containing a pharmaceutical
`
`composition and instructions for dosing, and preloaded composition and instructions for dosing, and preloaded
`
`syringes containing pharmaceutical compositions are also syringes containing pharmaceutical compositions are also
`
`encompassed by the invention. encompassed by the invention.
`
`
`
`6 Claims, 6 Drawing Sheets 6 Claims, 6 Drawing Sheets
`
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`

`

`US 8,911,737 B2 US 8,911,737 B2
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`
`Page 2 Page 2
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`Patients With Early, Aggressive Rheumatoid Arthritis Who Had Not Patients With Early, Aggressive Rheumatoid Arthritis Who Had Not
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`Burmester et al., 2002, "Long-Term Efficiacy and Safety of Burmester et al., 2002, "Long-Term Efficiacy and Safety of
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`fractory Rheumatoid Arthritis (cid:9) ResultsFrom a 2-Year Study," fractory Rheumatoid Arthritis (cid:9) ResultsFrom a 2-Year Study,"
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`Arthritis Rheum 46(Supp1 9):S537. Arthritis Rheum 46(Supp1 9):S537.
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`Burmester et al., 2013, "Efficacy, Pharmacokinetics, and Safety of Burmester et al., 2013, "Efficacy, Pharmacokinetics, and Safety of
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`(abstract 0P0067). (abstract 0P0067).
`
`

`

`US 8,911,737 B2 US 8,911,737 B2
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`Page 3 Page 3
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`(56) (cid:9)(56) (cid:9)
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`
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