Methods of administering anti-tnfalpha antibodies

Abstract

Methods of treating disorders in which TNFα activity is detrimental via biweekly, subcutaneous administration of human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor α (hTNFα) are disclosed. The antibody may be administered with or without methotrexate. These antibodies have high affinity for hTNFα (e.g., Kd=10−8 M or less), a slow off rate for hTNFα dissociation (e.g., Koff=10−3 sec−1 or less) and neutralize hTNFα activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Kits containing a pharmaceutical composition and instructions for dosing, and preloaded syringes containing pharmaceutical compositions are also encompassed by the invention.

What is claimed: 
     
         1 . A method for treating rheumatoid arthritis in a human subject, comprising administering subcutaneously to a human subject having rheumatoid arthritis a total body dose of 40 mg of a human anti-TNFα antibody once every 14 days for a time period sufficient to treat the rheumatoid arthritis, wherein the anti-TNFα antibody comprises an IgG1 heavy chain constant region; a variable light (“V L ”) chain region comprising a CDR1 having the amino acid sequence of SEQ ID NO:7, a CDR2 having the amino acid sequence of SEQ ID NO:5, and a CDR3 having the amino acid sequence of SEQ ID NO:3; and a variable heavy (“V H ”) chain region comprising a CDR1 having the amino acid sequence of SEQ ID NO:8, a CDR2 having the amino acid sequence of SEQ ID NO:6 and a CDR3 having the amino acid sequence of SEQ ID NO:4. 
     
     
         2 . The method of  claim 1 , wherein the V L  chain region of the anti-TNFα antibody has the amino acid sequence of SEQ ID NO:1 and the V H  chain region of the anti-TNFα antibody has the amino acid sequence of SEQ ID NO:2. 
     
     
         3 . The method of  claim 2 , wherein the anti-TNFα antibody is administered for a period of at least 24 weeks. 
     
     
         4 . The method of  claim 1 , wherein the anti-TNFα antibody is administered for a period of at least 24 weeks. 
     
     
         5 . A method for treating rheumatoid arthritis in a human subject, consisting of administering subcutaneously to a human subject having rheumatoid arthritis a composition comprising 40 mg of a human anti-TNFα antibody once every 14 days for a time period sufficient to treat the rheumatoid arthritis, wherein the anti-TNFα antibody comprises an IgG1 heavy chain constant region; a variable light (“V L ”) chain region comprising a CDR1 having the amino acid sequence of SEQ ID NO:7, a CDR2 having the amino acid sequence of SEQ ID NO:5, and a CDR3 having the amino acid sequence of SEQ ID NO:3; and a variable heavy (“V H ”) chain region comprising a CDR1 having the amino acid sequence of SEQ ID NO:8, a CDR2 having the amino acid sequence of SEQ ID NO:6 and a CDR3 having the amino acid sequence of SEQ ID NO:4, and wherein the human anti-TNFα antibody is administered in the form of a pharmaceutically acceptable composition. 
     
     
         6 . A method of reducing signs and symptoms in a patient with moderately to severely active rheumatoid arthritis, comprising:
 administering to said patient a total body dose of 40 mg of a human anti-TNFα antibody,   wherein the dose is administered subcutaneously from a 40 mg dosage unit form once every 14 days, and   wherein the anti-TNFα antibody comprises an IgG1 heavy chain constant region; a variable light (“V L ”) chain region comprising a CDR1 having the amino acid sequence of SEQ ID NO:7, a CDR2 having the amino acid sequence of SEQ ID NO:5, and a CDR3 having the amino acid sequence of SEQ ID NO:3; and a variable heavy (“V H ”) chain region comprising a CDR1 having the amino acid sequence of SEQ ID NO:8, a CDR2 having the amino acid sequence of SEQ ID NO:6 and a CDR3 having the amino acid sequence of SEQ ID NO:4.   
     
     
         7 . The method of  claim 6 , wherein the V L  chain region of the anti-TNFα antibody has the amino acid sequence of SEQ ID NO:1 and the V H  chain region of the anti-TNFα antibody has the amino acid sequence of SEQ ID NO:2. 
     
     
         8 . A method of reducing signs and symptoms in a patient with moderately to severely active rheumatoid arthritis, comprising:
 administering to said patient, in combination with methotrexate, a human anti-TNFα antibody,   wherein the human anti-TNFα antibody is administered subcutaneously in a total body dose of 40 mg once every 14 days, and   wherein the anti-TNFα antibody comprises an IgG1 heavy chain constant region; a variable light (“V L ”) chain region comprising a CDR1 having the amino acid sequence of SEQ ID NO:7, a CDR2 having the amino acid sequence of SEQ ID NO:5, and a CDR3 having the amino acid sequence of SEQ ID NO:3; and a variable heavy (“V H ”) chain region comprising a CDR1 having the amino acid sequence of SEQ ID NO:8, a CDR2 having the amino acid sequence of SEQ ID NO:6 and a CDR3 having the amino acid sequence of SEQ ID NO:4.   
     
     
         9 . The method of  claim 8 , wherein the V L  chain region of the anti-TNFα antibody has the amino acid sequence of SEQ ID NO:1 and the V H  chain region of the anti-TNFα antibody has the amino acid sequence of SEQ ID NO:2. 
     
     
         10 . The method of  claim 8 , wherein the dosage is administered from a 40 mg dosage unit form. 
     
     
         11 . The method of  claim 10 , wherein the V L  chain region of the anti-TNFα antibody has the amino acid sequence of SEQ ID NO:1 and the V H  chain region of the anti-TNFα antibody has the amino acid sequence of SEQ ID NO:2.