Integrin antagonists with enhanced antibody dependent...

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 16/00 (2006.01) A61K 39/395 (2006.01) A61K 39/40 (2006.01) C07K 1/00 (2006.01) C07K 14/00 (2006.01) C12N 15/00 (2006.01) C12P 21/06 (2006.01) C12P 21/08 (2006.01) C12Q 1/68 (2006.01)

Patent

CA 2577370

The present invention relates to novel Fc variants of antibodies that immuno- specifically binds to Integrin .alpha.V.beta.3. The Fc variants comprise a variable region that immunospecifically binds to Integrin .alpha.V.beta.3 and a Fc region that further comprises at least one novel amino acid residue which may provide for enhanced effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more Fc.gamma.R and/or C 1 q. Additionally, the Fc variants have altered antibody dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variants of an antibody that immunospecifically binds to Integrin .alpha.V.beta.3, particularly for therapeutic purposes.

L'invention concerne de nouveaux variants Fc d'anticorps qui se lient de façon immunospécifique à l'intégrine a<SB>V</SB>ß3. Les variants Fc comprennent une région variable qui se lie de façon immunospécifique à l'intégrine a<SB>V</SB>ß3 et une région Fc qui comprend également au moins un nouveau résidu d'aminoacide pouvant posséder une fonction effectrice améliorée. Plus spécifiquement, l'invention concerne des variants Fc qui présentent une affinité de liaison modifiée pour un ou plusieurs Fc.gamma.R et/ou C1q. De plus, les variants Fc présentent une cytotoxicité à médiation cellulaire dépendante de l'anticorps (ADCC) modifiée et/ou une action à cytotoxicité dépendante du complément (CDC). Par ailleurs, l'invention concerne des procédés et des protocoles d'application desdits variants Fc d'un anticorps qui se lient de façon immunospécifique à l'intégrine a<SB>V</SB>ß3, particulièrement à des fins thérapeutiques.

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