Human antibodies that bind human tnf.alpha.

Details Human antibodies that bind human tnf.alpha. Human antibodies that bind human tnf.alpha.

C - Chemistry, Metallurgy

12

N

C12N 15/13 (2006.01) A61K 39/395 (2006.01) C07K 16/24 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2243459

Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor .alpha. (hTNF.alpha.) are disclosed. These antibodies have high affinity for hTNF.alpha.(e.g., Kd = 10-8 M or less), a slow off rate for hTNF.alpha. dissociation (e.g., Koff = 10-3sec-1 or less) and neutralize hTNF.alpha. activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNF.alpha. and for inhibiting hTNF.alpha. activity, e.g., in a human subject suffering from a disorder in which hTNF.alpha. activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

L'invention concerne des anticorps humains, de préférence des anticorps humains de recombinaison, se fixant spécifiquement au facteur humain nécrosant des tumeurs de type .alpha. (hTNF.alpha.). Ces anticorps ont une affinité élevé pour le facteur hTNF.alpha. (par exemple K¿d? = 10?-8¿ M ou moins), une constante de vitesse de dissociation basse (par exemple K¿off? = 10?-3¿ sec?-1¿ ou moins) et ils neutralisent l'activité du facteur hTNF.alpha. in vitro et in vivo. L'anticorps de l'invention peut être un anticorps complet ou une partie de celui-ci se fixant à l'antigène. Les anticorps ou parties d'anticorps de l'invention sont utiles pour détecter le facteur hTNF.alpha. et pour inhiber l'activité du facteur hTNF.alpha., par exemple chez un sujet humain souffrant de troubles dans lesquels l'activité du facteur hTNF.alpha. est néfaste. L'invention concerne aussi les acides nucléiques, les vecteurs et les cellules hôtes exprimant les anticorps humains de recombinaison, ainsi que des méthodes de synthèse de ces anticorps humains de recombinaison.

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