111111111111111011111 Hill uuiJ111)11111111111111111111111111111
`
`USOO8889135B2
`
`(12) United States Patent (cid:9)
`(12) United States Patent
`Fischkoff et al. (cid:9)
`Fischkoff et a1.
`
`(10) Patent No.: (cid:9)
`(10) Patent N0.:
`(45) Date of Patent: (cid:9)
`(45) Date of Patent:
`
`US 8,889,135 B2
`US 8,889,135 B2
`Nov. 18, 2014
`Nov. 18, 2014
`
`(54)
`(54)
`
`METHODS OF ADMINISTERING ANTI-TNFa
`METHODS OF ADMINISTERING ANTI-TNFa
`ANTIBODIES
`ANTIBODIES
`
`(75)
`(75)
`
`Inventors: (cid:9) 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)
`(73)
`
`Assignee: Abeie Biotechnology Ltd., Hamilton
`Assignee: AbbVie Biotechnology Ltd., Hamilton
`(BM)
`(BM)
`
`(*)
`( * )
`
`Notice: (cid:9)
`Notice:
`
`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 944 days.
`U.S.C. 154(b) by 944 days.
`
`(21)
`(21)
`
`(22)
`(22)
`
`(65)
`(65)
`
`Appl. No.: 10/163,657
`Appl. No.: 10/163,657
`
`Filed:
`Filed: (cid:9)
`
`Jun. 5, 2002
`Jun. 5, 2002
`
`Prior Publication Data
`Prior Publication Data
`
`US 2003/0235585 Al (cid:9)
`US 2003/0235585 A1
`
`Dec. 25, 2003
`Dec. 25, 2003
`
`Related U.S. Application Data
`Related US. Application Data
`
`(60)
`(60) Provisional application No. 60/296,961, filed on Jun.
`Provisional application No. 60/296,961, ?led on Jun.
`8, 2001.
`8, 2001.
`
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`
`(51)
`(51) Int. Cl.
`Int. Cl.
`A61K 39/395 (cid:9)
`A61K 39/395
`C07K 16/24 (cid:9)
`C07K 16/24
`A61K 39/00 (cid:9)
`A61K 39/00
`(52)
`(52) U.S. Cl.
`US. Cl.
`C07K 16/241 (2013.01); A61K 39/3955
`CPC (cid:9)
`CPC ......... .. C07K16/241 (2013.01); A61K39/3955
`(2013.01); C07K 2317/76 (2013.01); A61K
`(2013.01); C07K 2317/76 (2013.01); A61K
`2300/00 (2013.01); A61K 2039/505 (2013.01);
`2300/00 (2013.01); A61K 2039/505 (2013.01);
`A61K 2039/545 (2013.01); A61K 2039/54
`A61K 2039/545 (2013.01); A61K 2039/54
`(2013.01); C07K 2317/21 (2013.01)
`(2013.01); C07K 2317/2] (2013.01)
` 424/145.1
`USPC (cid:9)
`USPC ..................................................... .. 424/145.1
`(58) Field of Classification Search
`(58)
`Field of Classi?cation Search
`None
`None
`See application ?le for complete search history.
`See application file for complete search history.
`
`(56)
`(56)
`
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`(Continued)
`(Continued)
`
`FOREIGN PATENT DOCUMENTS
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`
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`2/1998
`2261630
`(Continued)
`(Continued)
`OTHER PUBLICATIONS
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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
`
`ABSTRACT
`(57)
`ABSTRACT
`(57) (cid:9)
`Methods of treating disorders in Which TFNO. activity is
`Methods of treating disorders in which TFNa 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 speci?cally bind to human tumor necrosis factor (X
`(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
`a?inity for hTNFa (e.g., KflO'8 M or less), a sloW off rate
`for hTNFa dissociation (e.g., Koc10-3 sec-' or less) and
`for hTNFa dissociation (e.g., KOfI10—3 sec‘1 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.
`
`5 Claims, 6 Drawing Sheets
`5 Claims, 6 Drawing Sheets
`
`(cid:9)
`(cid:9)
`(cid:9)
`

`

`US 8,889,135 B2
`US 8,889,135 B2
`Page 2
`Page 2
`
`(56)
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