Optimized proteins that target the epidermal growth factor receptor
First Claim
Patent Images
1. An anti-human EGFR antibody that comprises a variant human immunoglobulin G constant region comprising a sequence having the formula:
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Vx(222)-Vx(223)-Vx(224)-Vx(225)-Fx(226)-Vx(227)-Vx(228)-Fx(229)-Vx(230)-Fx(231)-Vx(232)-Vx(233)-Vx(234)-Vx(235)-Vx(236)-Vx(237)-Vx(238)-Vx(239)-Vx(240)-Vx(241)-Fx(242)-Vx(243)-Vx(244)-Vx(245)-Vx(246)-Vx(247)-Fx(248-254)-Vx(255)-Fx(256-257)-Vx(258)-Fx(259)-Vx(260)-Fx(261)-Vx(262)-Vx(263)-Vx(264)-Vx(265)-Vx(266)-Vx(267)-Vx(268)-Vx(269)-Vx(270)-Vx(271)-Vx(272)-Vx(273)-Vx(274)-Vx(274)-Vx(275)-Vx(276)-Fx(277)-Vx(278)-Fx(279)-Vx(280)-Vx(281)-Vx(282)-Vx(283)-Vx(284)-Vx(285)-Vx(286)-Fx(287)-Vx(288)-Fx(289)-Vx(290)-Vx(291)-Vx(292)-Vx293)-Vx(294)-Vx(295)-Vx(296)-Vx(297)-Vx(298)-Vx(299)-Vx(300)-Vx(301)-Vx(302)-Vx(303)-Vx(304)-Vx(305)-Fx(306-312)-Vx(313)-Fx(314-316)-Vx(317)-Vx(318)-Fx(319)-Vx(320)-Fx(321)-Vx(322)-Vx(323)-Vx(324)-Vx(325)-Vx(326)-Fx(327)-Vx(328)-Vx(329)-Fx(330)-Vx(331)-Vx(332)-Vx(333)-Vx(334)-Vx(335)-Vx(336)-Vx(337)-Fx(338-447) wherein Vx(222) is an amino acid selected from the group consisting of K, E and Y;
Vx(223) is an amino acid selected from the group consisting of T, E and K;
Vx(224) is an amino acid selected from the group consisting of H, E and Y;
Vx(225) is an amino acid selected from the group consisting of T, E, K and W;
Fx(226) is the human wild-type IgG1 sequence at position 226;
Vx(227) is an amino acid selected from the group consisting of P, E, G, K and Y;
Vx(228) is an amino acid selected from the group consisting of P, E, G, K and Y;
Fx(229) is the human wild-type IgG1 sequence at position 229;
Vx(230) is an amino acid selected from the group consisting of P, A, E, G and Y;
Fx(231) is the human wild-type IgG1 sequence at position 231;
Vx(232) is an amino acid selected from the group consisting of P, E, G, K and Y;
Vx(233) is an amino acid selected from the group consisting of E, A, D, F, G, H, I, K, L, M, N, Q, R, S, T, V, W and Y;
Vx(234) is an amino acid selected from the group consisting of L, A, D, E, F, G, H, I, K, M, N, P, Q, R, S, T, V, W and Y;
Vx(235) is an amino acid selected from the group consisting of L, A, D, E, F, G, H, I, K, M, N, P, Q, R, S, T, V, W and Y;
Vx(236) is an amino acid selected from the group consisting of G, A, D, E, F, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y;
Vx(237) is an amino acid selected from the group consisting of G, D, E, F, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y;
Vx(238) is an amino acid selected from the group consisting of P, D, E, F, G, H, I, K, L, M, N, Q, R, S, T, V, W and Y;
Vx(239) is an amino acid selected from the group consisting of S, D, E, F, G, H ,I ,K, L, M, N, P, Q, R, T, V, W and Y;
Vx(240) is an amino acid selected from the group consisting of V, A, I, M and T;
Vx(241) is an amino acid selected from the group consisting of F, D, E, L, R, W and Y;
Fx(242) is the human wild-type IgG1 sequence at position 242;
Vx(243) is an amino acid selected from the group consisting of F, E, L, Q, R, W and Y;
Vx(244) is an amino acid selected from the group consisting of P and H;
Vx(245) is an amino acid selected from the group consisting of P and A;
Vx(246) is an amino acid selected from the group consisting of K, D, E, H and Y;
Vx(247) is an amino acid selected from the group consisting of P, G and V;
Fx(248-254) is the human wild-type IgG1 sequence at positions 248-254;
Vx(255) is an amino acid selected from the group consisting of R, E and Y;
Fx(256-257) is the human wild-type IgG1 sequence at positions 256-257;
Vx(258) is an amino acid selected from the group consisting of E, H, S and Y;
Fx(259) is the human wild-type IgG1 sequence at position 259;
Vx(260) is an amino acid selected from the group consisting of T, D, E, H and Y;
Fx(261) is the human wild-type IgG1 sequence at position 261;
Vx(262) is an amino acid selected from the group consisting of V, A, E, F, I and T;
Vx(263) is an amino acid selected from the group consisting of V, A, I, M and T;
Vx(264) is an amino acid selected from the group consisting of V, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, W and Y;
Vx(265) is an amino acid selected from the group consisting of D, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y;
Vx(266) is an amino acid selected from the group consisting of V, A, I, M and T;
Vx(267) is an amino acid selected from the group consisting of S, D, E, F, H, I, K, L, M, N, P, Q, R, T, V, W and Y;
Vx(268) is an amino acid selected from the group consisting of H, D, E, F, G, I, K, L, M, P, Q, R, T, V and W;
Vx(269) is an amino acid selected from the group consisting of E, F, G, H, I, K, L, M, N, P, R, S, T, V, W and Y;
Vx(270) is an amino acid selected from the group consisting of D, F, G, H, I, L, M, P, Q, R, S, T, W and Y;
Vx(271) is an amino acid selected from the group consisting of P, A, D, E, F, G, H, I, K, L, M, N, Q, R, S, T, V, W and Y;
Vx(272) is an amino acid selected from the group consisting of E, D, F, G, H, I, K, L, M, P, R, S, T, V, W and Y;
Vx(273) is an amino acid selected from the group consisting of V and I;
Vx(274) is an amino acid selected from the group consisting of K, D, E, F, G, H, I, L, M, N, P, R, S, T, V, W and Y;
Vx(275) is an amino acid selected from the group consisting of F, L and W;
Vx(276) is an amino acid selected from the group consisting of N, D, E, F, G, H, I, L, M, P, R, S, T, V, W and Y;
Fx(277) is the human wild-type IgG1 sequence at position 277;
Vx(278) is an amino acid selected from the group consisting of Y, D, E, G, H, I, K, L, M, N, P, Q, R, S, T, V and W;
Fx(279) is the human wild-type IgG1 sequence at position 279;
Vx(280) is an amino acid selected from the group consisting of D, G, K, L, P and W;
Vx(281) is an amino acid selected from the group consisting of G, D, K, P and Y;
Vx(282) is an amino acid selected from the group consisting of V, E, G, K, P and Y;
Vx(283) is an amino acid selected from the group consisting of E, G, H, K, L, P, R and Y;
Vx(284) is an amino acid selected from the group consisting of V, E, L, N, T and Y;
Vx(285) is an amino acid selected from the group consisting of H, D, E, K, Q, W and Y;
Vx(286) is an amino acid selected from the group consisting of N, E, G, P and Y;
Fx(287) is the human wild-type IgG1 sequence at position 287;
Vx(288) is an amino acid selected from the group consisting of K, D, E and Y;
Fx(289) is the human wild-type IgG1 sequence at position289;
Vx(290) is an amino acid selected from the group consisting of K, D, H, L, N and W;
Vx(291) is an amino acid selected from the group consisting of P, D, E, G, H, I, Q and T;
Vx(292) is an amino acid selected from the group consisting of R, D, E, T and Y;
Vx(293) is an amino acid selected from the group consisting of E, F, G, H, I, L, M, N, P, R, S, T, V, W and Y;
Vx(294) is an amino acid selected from the group consisting of E, F, G, H, I, K, L, M, P, R, S, T, V, W and Y;
Vx(295) is an amino acid selected from the group consisting of Q, D, E, F, G, H, I, M, N, P, R, S, T, V, W and Y;
Vx(296) is an amino acid selected from the group consisting of Y, A, D, E, G, H, I, K, L, M, N, Q, R, S, T and V;
Vx(297) is an amino acid selected from the group consisting of N, D, E, F, G, H, I, K, L, M, P, Q, R, S, T, V, W and Y;
Vx(298) is an amino acid selected from the group consisting of S, D, E, F, I, K, M, Q, R, W and Y;
Vx(299) is an amino acid selected from the group consisting of T, A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, V, W and Y;
Vx(300) is an amino acid selected from the group consisting of Y, A, D, E, G, H, K, M, N, P, Q, R, S, T, V and W;
Vx(301) is an amino acid selected from the group consisting of R, D, E, H and Y;
Vx(302) is an amino acid selected from the group consisting of V and I;
Vx(303) is an amino acid selected from the group consisting of V, D, E and Y;
Vx(304) is an amino acid selected from the group consisting of S, D, H, L, N and T;
Vx(305) is an amino acid selected from the group consisting of V, E, T and Y;
Fx(306-312) is the human wild-type IgG1 sequence at positions 306-312;
Vx(313) is an amino acid selected from the group consisting of W and F;
Fx(314-316) is the human wild-type IgG1 sequence at positions 314-316;
Vx(317) is an amino acid selected from the group consisting of K E and Q;
Vx(318) is an amino acid selected from the group consisting of E, H, L, Q, R and Y;
Fx(319) is the human wild-type IgG1 sequence at position 319;
Vx(320) is an amino acid selected from the group consisting of K, D, F, G, H, I, L, N, P, S, T, V, W and Y;
Fx(321) is the human wild-type IgG1 sequence at position 321;
Vx(322) is an amino acid selected from the group consisting of K, D, F, G, H, I, P, S, T, V, W and Y;
Vx(323) is an amino acid selected from the group consisting of V and I;
Vx(324) is an amino acid selected from the group consisting of S, D, F, G, H, I, L, M, P, R, T, V, W and Y;
Vx(325) is an amino acid selected from the group consisting of N, A, D, E, F, G, H, I, K, L, M, P, Q, R, S, T, V, W and Y;
Vx(326) is an amino acid selected from the group consisting of K, I, L, P and T;
Fx(327) is the human wild-type IgG1 sequence at position 327 Vx(328) is an amino acid selected from the group consisting of L, A, D, E, F, G, H. I, K, M, N, P, Q, R, S, T, V, W and Y;
Vx(329) is an amino acid selected from the group consisting of P, D, E, F, G, H. 1, K, L, M, N, Q, R, S, T, V, W and Y;
Fx(330) is the human wild-type IgG1 sequence at position330;
Vx(331) is an amino acid selected from the group consisting of P, D, F, H, I, L, M, Q, R, T, V, W and Y;
Vx(332) is an amino acid selected from the group consisting of I, A, D, E, F, G, H, K, L, M, N, P, Q, R, S, T, V, W and Y;
Vx(333) is an amino acid selected from the group consisting of E, F, H, I, L, M, P, T and Y;
Vx(334) is an amino acid selected from the group consisting of K, F, I, P and T;
Vx(335) is an amino acid selected from the group consisting of T, D, F, G, H, I, L, M, N, P, R, S, V, W and Y;
Vx(336) is an amino acid selected from the group consisting of I, E, K and Y;
Vx(337) is an amino acid selected from the group consisting of S, E, H and N;
Fx(338-447) is the human wild-type IgG1 sequence at positions 338-447;
wherein at least one amino acid is substituted as compared to the wild-type sequence (SEQ ID NO;
X), and wherein said antibody has an altered property, said property selected from the group consisting of altered Fcγ
R binding and altered effector function.
1 Assignment
0 Petitions
Accused Products
Abstract
The present invention relates to optimized proteins that target the Epidermal Growth Factor Receptor (EGFR), and their application, particularly for therapeutic purposes.
162 Citations
6 Claims
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1. An anti-human EGFR antibody that comprises a variant human immunoglobulin G constant region comprising a sequence having the formula:
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Vx(222)-Vx(223)-Vx(224)-Vx(225)-Fx(226)-Vx(227)-Vx(228)-Fx(229)-Vx(230)-Fx(231)-Vx(232)-Vx(233)-Vx(234)-Vx(235)-Vx(236)-Vx(237)-Vx(238)-Vx(239)-Vx(240)-Vx(241)-Fx(242)-Vx(243)-Vx(244)-Vx(245)-Vx(246)-Vx(247)-Fx(248-254)-Vx(255)-Fx(256-257)-Vx(258)-Fx(259)-Vx(260)-Fx(261)-Vx(262)-Vx(263)-Vx(264)-Vx(265)-Vx(266)-Vx(267)-Vx(268)-Vx(269)-Vx(270)-Vx(271)-Vx(272)-Vx(273)-Vx(274)-Vx(274)-Vx(275)-Vx(276)-Fx(277)-Vx(278)-Fx(279)-Vx(280)-Vx(281)-Vx(282)-Vx(283)-Vx(284)-Vx(285)-Vx(286)-Fx(287)-Vx(288)-Fx(289)-Vx(290)-Vx(291)-Vx(292)-Vx293)-Vx(294)-Vx(295)-Vx(296)-Vx(297)-Vx(298)-Vx(299)-Vx(300)-Vx(301)-Vx(302)-Vx(303)-Vx(304)-Vx(305)-Fx(306-312)-Vx(313)-Fx(314-316)-Vx(317)-Vx(318)-Fx(319)-Vx(320)-Fx(321)-Vx(322)-Vx(323)-Vx(324)-Vx(325)-Vx(326)-Fx(327)-Vx(328)-Vx(329)-Fx(330)-Vx(331)-Vx(332)-Vx(333)-Vx(334)-Vx(335)-Vx(336)-Vx(337)-Fx(338-447)wherein Vx(222) is an amino acid selected from the group consisting of K, E and Y;
Vx(223) is an amino acid selected from the group consisting of T, E and K;
Vx(224) is an amino acid selected from the group consisting of H, E and Y;
Vx(225) is an amino acid selected from the group consisting of T, E, K and W;
Fx(226) is the human wild-type IgG1 sequence at position 226;
Vx(227) is an amino acid selected from the group consisting of P, E, G, K and Y;
Vx(228) is an amino acid selected from the group consisting of P, E, G, K and Y;
Fx(229) is the human wild-type IgG1 sequence at position 229;
Vx(230) is an amino acid selected from the group consisting of P, A, E, G and Y;
Fx(231) is the human wild-type IgG1 sequence at position 231;
Vx(232) is an amino acid selected from the group consisting of P, E, G, K and Y;
Vx(233) is an amino acid selected from the group consisting of E, A, D, F, G, H, I, K, L, M, N, Q, R, S, T, V, W and Y;
Vx(234) is an amino acid selected from the group consisting of L, A, D, E, F, G, H, I, K, M, N, P, Q, R, S, T, V, W and Y;
Vx(235) is an amino acid selected from the group consisting of L, A, D, E, F, G, H, I, K, M, N, P, Q, R, S, T, V, W and Y;
Vx(236) is an amino acid selected from the group consisting of G, A, D, E, F, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y;
Vx(237) is an amino acid selected from the group consisting of G, D, E, F, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y;
Vx(238) is an amino acid selected from the group consisting of P, D, E, F, G, H, I, K, L, M, N, Q, R, S, T, V, W and Y;
Vx(239) is an amino acid selected from the group consisting of S, D, E, F, G, H ,I ,K, L, M, N, P, Q, R, T, V, W and Y;
Vx(240) is an amino acid selected from the group consisting of V, A, I, M and T;
Vx(241) is an amino acid selected from the group consisting of F, D, E, L, R, W and Y;
Fx(242) is the human wild-type IgG1 sequence at position 242;
Vx(243) is an amino acid selected from the group consisting of F, E, L, Q, R, W and Y;
Vx(244) is an amino acid selected from the group consisting of P and H;
Vx(245) is an amino acid selected from the group consisting of P and A;
Vx(246) is an amino acid selected from the group consisting of K, D, E, H and Y;
Vx(247) is an amino acid selected from the group consisting of P, G and V;
Fx(248-254) is the human wild-type IgG1 sequence at positions 248-254;
Vx(255) is an amino acid selected from the group consisting of R, E and Y;
Fx(256-257) is the human wild-type IgG1 sequence at positions 256-257;
Vx(258) is an amino acid selected from the group consisting of E, H, S and Y;
Fx(259) is the human wild-type IgG1 sequence at position 259;
Vx(260) is an amino acid selected from the group consisting of T, D, E, H and Y;
Fx(261) is the human wild-type IgG1 sequence at position 261;
Vx(262) is an amino acid selected from the group consisting of V, A, E, F, I and T;
Vx(263) is an amino acid selected from the group consisting of V, A, I, M and T;
Vx(264) is an amino acid selected from the group consisting of V, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, W and Y;
Vx(265) is an amino acid selected from the group consisting of D, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y;
Vx(266) is an amino acid selected from the group consisting of V, A, I, M and T;
Vx(267) is an amino acid selected from the group consisting of S, D, E, F, H, I, K, L, M, N, P, Q, R, T, V, W and Y;
Vx(268) is an amino acid selected from the group consisting of H, D, E, F, G, I, K, L, M, P, Q, R, T, V and W;
Vx(269) is an amino acid selected from the group consisting of E, F, G, H, I, K, L, M, N, P, R, S, T, V, W and Y;
Vx(270) is an amino acid selected from the group consisting of D, F, G, H, I, L, M, P, Q, R, S, T, W and Y;
Vx(271) is an amino acid selected from the group consisting of P, A, D, E, F, G, H, I, K, L, M, N, Q, R, S, T, V, W and Y;
Vx(272) is an amino acid selected from the group consisting of E, D, F, G, H, I, K, L, M, P, R, S, T, V, W and Y;
Vx(273) is an amino acid selected from the group consisting of V and I;
Vx(274) is an amino acid selected from the group consisting of K, D, E, F, G, H, I, L, M, N, P, R, S, T, V, W and Y;
Vx(275) is an amino acid selected from the group consisting of F, L and W;
Vx(276) is an amino acid selected from the group consisting of N, D, E, F, G, H, I, L, M, P, R, S, T, V, W and Y;
Fx(277) is the human wild-type IgG1 sequence at position 277;
Vx(278) is an amino acid selected from the group consisting of Y, D, E, G, H, I, K, L, M, N, P, Q, R, S, T, V and W;
Fx(279) is the human wild-type IgG1 sequence at position 279;
Vx(280) is an amino acid selected from the group consisting of D, G, K, L, P and W;
Vx(281) is an amino acid selected from the group consisting of G, D, K, P and Y;
Vx(282) is an amino acid selected from the group consisting of V, E, G, K, P and Y;
Vx(283) is an amino acid selected from the group consisting of E, G, H, K, L, P, R and Y;
Vx(284) is an amino acid selected from the group consisting of V, E, L, N, T and Y;
Vx(285) is an amino acid selected from the group consisting of H, D, E, K, Q, W and Y;
Vx(286) is an amino acid selected from the group consisting of N, E, G, P and Y;
Fx(287) is the human wild-type IgG1 sequence at position 287;
Vx(288) is an amino acid selected from the group consisting of K, D, E and Y;
Fx(289) is the human wild-type IgG1 sequence at position289;
Vx(290) is an amino acid selected from the group consisting of K, D, H, L, N and W;
Vx(291) is an amino acid selected from the group consisting of P, D, E, G, H, I, Q and T;
Vx(292) is an amino acid selected from the group consisting of R, D, E, T and Y;
Vx(293) is an amino acid selected from the group consisting of E, F, G, H, I, L, M, N, P, R, S, T, V, W and Y;
Vx(294) is an amino acid selected from the group consisting of E, F, G, H, I, K, L, M, P, R, S, T, V, W and Y;
Vx(295) is an amino acid selected from the group consisting of Q, D, E, F, G, H, I, M, N, P, R, S, T, V, W and Y;
Vx(296) is an amino acid selected from the group consisting of Y, A, D, E, G, H, I, K, L, M, N, Q, R, S, T and V;
Vx(297) is an amino acid selected from the group consisting of N, D, E, F, G, H, I, K, L, M, P, Q, R, S, T, V, W and Y;
Vx(298) is an amino acid selected from the group consisting of S, D, E, F, I, K, M, Q, R, W and Y;
Vx(299) is an amino acid selected from the group consisting of T, A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, V, W and Y;
Vx(300) is an amino acid selected from the group consisting of Y, A, D, E, G, H, K, M, N, P, Q, R, S, T, V and W;
Vx(301) is an amino acid selected from the group consisting of R, D, E, H and Y;
Vx(302) is an amino acid selected from the group consisting of V and I;
Vx(303) is an amino acid selected from the group consisting of V, D, E and Y;
Vx(304) is an amino acid selected from the group consisting of S, D, H, L, N and T;
Vx(305) is an amino acid selected from the group consisting of V, E, T and Y;
Fx(306-312) is the human wild-type IgG1 sequence at positions 306-312;
Vx(313) is an amino acid selected from the group consisting of W and F;
Fx(314-316) is the human wild-type IgG1 sequence at positions 314-316;
Vx(317) is an amino acid selected from the group consisting of K E and Q;
Vx(318) is an amino acid selected from the group consisting of E, H, L, Q, R and Y;
Fx(319) is the human wild-type IgG1 sequence at position 319;
Vx(320) is an amino acid selected from the group consisting of K, D, F, G, H, I, L, N, P, S, T, V, W and Y;
Fx(321) is the human wild-type IgG1 sequence at position 321;
Vx(322) is an amino acid selected from the group consisting of K, D, F, G, H, I, P, S, T, V, W and Y;
Vx(323) is an amino acid selected from the group consisting of V and I;
Vx(324) is an amino acid selected from the group consisting of S, D, F, G, H, I, L, M, P, R, T, V, W and Y;
Vx(325) is an amino acid selected from the group consisting of N, A, D, E, F, G, H, I, K, L, M, P, Q, R, S, T, V, W and Y;
Vx(326) is an amino acid selected from the group consisting of K, I, L, P and T;
Fx(327) is the human wild-type IgG1 sequence at position 327 Vx(328) is an amino acid selected from the group consisting of L, A, D, E, F, G, H. I, K, M, N, P, Q, R, S, T, V, W and Y;
Vx(329) is an amino acid selected from the group consisting of P, D, E, F, G, H. 1, K, L, M, N, Q, R, S, T, V, W and Y;
Fx(330) is the human wild-type IgG1 sequence at position330;
Vx(331) is an amino acid selected from the group consisting of P, D, F, H, I, L, M, Q, R, T, V, W and Y;
Vx(332) is an amino acid selected from the group consisting of I, A, D, E, F, G, H, K, L, M, N, P, Q, R, S, T, V, W and Y;
Vx(333) is an amino acid selected from the group consisting of E, F, H, I, L, M, P, T and Y;
Vx(334) is an amino acid selected from the group consisting of K, F, I, P and T;
Vx(335) is an amino acid selected from the group consisting of T, D, F, G, H, I, L, M, N, P, R, S, V, W and Y;
Vx(336) is an amino acid selected from the group consisting of I, E, K and Y;
Vx(337) is an amino acid selected from the group consisting of S, E, H and N;
Fx(338-447) is the human wild-type IgG1 sequence at positions 338-447;
wherein at least one amino acid is substituted as compared to the wild-type sequence (SEQ ID NO;
X), and wherein said antibody has an altered property, said property selected from the group consisting of altered Fcγ
R binding and altered effector function.- View Dependent Claims (2, 3, 4, 5, 6)
Fx(222-238)-Vx(239)-Fx(240-263)-Vx(264)-Fx(265-329)-Vx(330)-Fx(331 )-Vx(332)-Fx(333-447)Wherein Fx(222-238) is the human wild-type IgG1 sequence at positions 222-238;
Vx(239) is an amino acid selected from the group consisting of S, D, E, F, G, H, I, K, L, M, N, P, Q, R, T, V, W and Y;
Fx(240-263) is the human wild-type IgG1 sequence at positions 240-263;
Vx(264) is an amino acid selected from the group consisting of V, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, W and Y;
Fx(265-329) is the human wild-type IgG1 sequence at positions 265-229;
Vx(330) is an amino acid selected from the group consisting of A, E, F, G, H, I, L, M, N, P, R, S, T, V, W and Y;
Fx(3
31) is the human wild-type IgG1 sequence at position 331;
Vx(332) is an amino acid selected from the group consisting of I, A, D, E, F, G, H, K, L, M, N, P, Q, R, S, T, V, W and Y Fx(333-447) is the human wild-type IgG1 sequence at positions 333-447;
And wherein at least one of said Vx amino acids is not the wild-type amino acid.
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3. An anti-human EGFR antibody according to claim 1 wherein said IgG region is an IgG2 region having the formula:
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Fx(222-232)-Vx(233)-Vx(234)-Vx(235)-Vx(236)-Fx(237-238)-Vx(239)-Fx(240-263)-Vx(264)-Fx(265-326)-Vx(327)-Fx(328-329)-Vx(330)-Fx(331 )-Vx(332)-Fx(333-447)Wherein Fx(222-232) is the human wild-type IgG2 sequence at positions 222-232;
Vx(233) is an amino acid selected from the group consisting of E, A, D, F, G, H, I, K, L, M, N, Q, R, S, T, V, W and Y;
Vx(234) is an amino acid selected from the group consisting of L, A, D, E, F, G, H, I, K, M, N, P, Q, R, S, T, V, W and Y;
Vx(235) is an amino acid selected from the group consisting of L, A, D, E, F, G, H, I, K, M, N, P, Q, R, S, T, V, W and Y;
Vx(236) is an amino acid deletion as compared to the EU Kabat sequence;
Fx(237-238) is the human wild-type IgG2 sequence at positions 237-238;
Vx(239) is an amino acid selected from the group consisting of S, D, E, F, G, H, I, K, L, M, N, P, Q, R, T, V, W and Y;
Fx(240-263) is the human wild-type IgG2 sequence at positions 240-263;
Vx(264) is an amino acid selected from the group consisting of V, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, W and Y;
Fx(265-326) is the human wild-type IgG2 sequence at positions 265-326;
Vx(327) is an amino acid selected from the group consisting of A, D, E, F, H, I, K, L, M, N, P, R, T, V, W and Y;
Fx(328-329) is the human wild-type IgG2 sequence at positions 328-329;
Vx(330) is an amino acid selected from the group consisting of A, E, F, G, H, I, L, M, N, P, R, S, T, V, W and Y;
Fx(3
31) is the human wild-type IgG2 sequence at position 331;
Vx(332) is an amino acid selected from the group consisting of I, A, D, E, F, G, H, K, L, M, N, P, Q, R, S, T, V, W and Y;
Fx(333-447) is the human wild-type IgG2 sequence at positions 333-447;
and wherein at least one of said Vx amino acids is not the wild-type amino acid.
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4. An antibody according to any of claims 1-3 wherein said antibody comprises said IgG region and a variable light region selected from the group consisting of C225 L0 (SEQ ID NO:
- 2), C225 L2 (SEQ ID NO;
7), C225 L3 (SEQ ID NO;
8), C225 L4 (SEQ ID NO;
9) and ICR62 L3 (SEQ ID NO;
16).
- 2), C225 L2 (SEQ ID NO;
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5. An antibody according to any of claims 1-4 wherein said antibody comprises said IgG region and a variable heavy region selected from the group consisting of C225 H0 (SEQ ID NO:
- 3, C225 H3 (SEQ ID NO;
10), C225 H4 (SEQ ID NO;
11), C225 H5 (SEQ ID NO;
12), C225 H6 (SEQ ID NO;
13), C225 H7 (SEQ ID NO;
14), C225 H8 (SEQ ID NO;
15), ICR62 H9 (SEQ ID NO;
17) and ICR62 H10 (SEQ ID NO;
18).
- 3, C225 H3 (SEQ ID NO;
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6. An antibody according to any of claims 1-5 wherein said antibody comprises an engineered glycoform.
Specification