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US 2006/0134105 A1Published application
IgG immunoglobulin variants with optimized effector function
AssigneeXencor, Inc.
InventorsGregory Lazar, Bassil Dahiyat, Wei Dang, Sher Karki, Omid Vafa
Life of this patent
Estimating the term…
Abstract
The present application relates to optimized IgG immunoglobulin variants, engineering methods for their generation, and their application, particularly for therapeutic purposes.
Claims4
An IgG2 variant comprising an amino acid sequence having the formula:
- ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT
- VPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCC-X(221)-X(222)-X(223)-X(224)-X(225)-C-X(227)-
- X(228)-C-X(230)-X(231)-X(232)-ELLGG-X(238)-X(239)-X(240)-X(241)-L-X(243)-X(244)-X(245)-X(246)-
- X(247)-K-X(249)-TLMIS-X(255)-TP-X(258)-V-X(260)-C-X(262)-X(263)-X(264)-X(265)-X(266)-X(267)-
- X(268)-X(269)-X(270)-X(271)-X(272)-X(273)-X(274)-X(275)-X(276)-W-X(278)-V-X(280)-X(281)-X(282)-
- X(283)-X(284)-X(285)-X(286)-A-X(288)-T-X(290)-X(291)-X(292)-X(293)-X(294)-X(295)-X(296)-X(297)-
- X(298)-X(299)-X(300)-X(301)-X(302)-X(303)-X(304)-X(305)-LTVVHQD-X(313)-LNG-X(317)-X(318)-Y-
- X(320)-C-X(322)-X(323)-X(324)-X(325)-X(326)-X(327)-X(328)-X(329)-X(330)-X(331)-X(332)-X(333)-
- X(334)-X(335)-X(336)-X(337)-
- KTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFL
- YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK-,
- wherein
- —X(221)—is selected from the group consisting of no amino acid, K and Y;
- —X(222)—is selected from the group consisting of V, E and Y;
- —X(223)—is selected from the group consisting of no amino acid, E and K;
- —X(224)—is selected from the group consisting of E and Y;
- —X(225)—is selected from the group consisting of no amino acid, E, K and W;
- —X(227)—is selected from the group consisting of P, E, G, K and Y;
- —X(228)—is selected from the group consisting of P, E, G, K and Y;
- —X(230)—is selected from the group consisting of P, A, E, G and Y;
- —X(231)—is selected from the group consisting of A, E, G, K, P and Y;
- —X(232)—is selected from the group consisting of P, E, G, K and Y;
- —X(233)—is selected from the group consisting of P, A, D, F, G, H, I, K, L, M, N, Q, R, S, T, V, W and Y;
- —X(234)—is selected from the group consisting of V, D, E, F, G, H, I, K, M, N, P, Q, R, S, T, W and Y;
- —X(235)—is selected from the group consisting of A, D, F, G, H, I, K, M, N, P, Q, R, S, T, V, W and Y;
- —X(236)—is selected from the group consisting of no amino acid, A, D, E, F, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y;
- —X(237)—is 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;
- —X(238)—is 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;
- —X(239)—is 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;
- —X(240)—is selected from the group consisting of V, A, I, M and T;
- —X(241)—is selected from the group consisting of F, D, E, L, R, S, W and Y;
- —X(243)—is selected from the group consisting of F, E, H, L, Q, R, W and Y;
- —X(244)—is selected from the group consisting of P and H;
- —X(245)—is selected from the group consisting of P and A;
- —X(246)—is selected from the group consisting of K, D, E, H and Y;
- —X(247)—is selected from the group consisting of P, G and V;
- —X(249)—is selected from the group consisting of D, H, Q and Y;
- —X(255)—is selected from the group consisting of R, E and Y;
- —X(258)—is selected from the group consisting of E, H, S and Y;
- —X(260)—is selected from the group consisting of T, D, E, H and Y;
- —X(262)—is selected from the group consisting of V, A, E, F, I and T;
- —X(263)—is selected from the group consisting of V, A, I, M and T;
- —X(264)—is selected from the group consisting of V, A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, W and Y;
- —X(265)—is selected from the group consisting of D, F, G, H, I, K, L, M, P, Q, R, S, T, V, W and Y;
- —X(266)—is selected from the group consisting of V, A, I, M and T;
- —X(267)—is selected from the group consisting of S, D, E, F, H, I, K, L, M, N, P, Q, R, V, W and Y;
- —X(268)—is selected from the group consisting of H, D, E, F, G, I, K, L, M, P, R, T, V and W;
- —X(269)—is selected from the group consisting of E, F, G, H, I, K, L, M, N, P, R, S, T, V, W and Y;
- —X(270)—is selected from the group consisting of D, F, G, H, I, L, M, P, Q, R, S, T, W and Y;
- —X(271)—is 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;
- —X(272)—is selected from the group consisting of E, D, F, G, H, I, K, L, M, P, R, S, T, V, W and Y;
- —X(273)—is selected from the group consisting of V and I;
- —X(274)—is selected from the group consisting of Q, D, E, F, G, H, i, L, M, N, P, R, T, V, W and Y;
- —X(275)—is selected from the group consisting of F, L and W;
- —X(276)—is selected from the group consisting of N, D, E, F, G, H, I, L, M, P, R, S, T, V, W and Y;
- —X(278)—is selected from the group consisting of Y, D, E, G, H, I, K, L, M, N, P, Q, R, S, T, V and W;
- —X(280)—is selected from the group consisting of D, G, K, L, P and W;
- —X(281)—is selected from the group consisting of G, D, E, K, N, P, Q and Y;
- —X(282)—is selected from the group consisting of V, E, G, K, P and Y;
- —X(283)—is selected from the group consisting of E, G, H, K, L, P, R and Y;
- —X(284)—is selected from the group consisting of V, D, E, L, N, Q, T and Y;
- —X(285)—is selected from the group consisting of H, D, E, K, Q, W and Y;
- —X(286)—is selected from the group consisting of N, E, G, P and Y;
- —X(288)—is selected from the group consisting of K, D, E and Y;
- —X(290)—is selected from the group consisting of K, D, H, L, N and W;
- —X(291)—is selected from the group consisting of P, D, E, G, H, I, Q and T;
- —X(292)—is selected from the group consisting of R, D, E, T and Y;
- —X(293)—is selected from the group consisting of E, F, G, H, I, L, M, N, P, R, S, T, V, W and Y;
- —X(294)—is selected from the group consisting of E, F, G, H, I, K, L, M, P, R, S, T, V, W and Y;
- —X(295)—is selected from the group consisting of Q, D, E, F, G, H, I, M, N, P, R, S, T, V, W and Y;
- —X(296)—is selected from the group consisting of F, A, D, E, G, I, K, L, M, N, Q, R, S, T and V;
- —X(297)—is 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;
- —X(298)—is selected from the group consisting of S, E, F, H, I, K, M, Q, R, W and Y;
- —X(299)—is 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;
- —X(300)—is selected from the group consisting of F, A, D, E, G, H, K, M, N, P, Q, R, S, T, V and W;
- —X(301)—is selected from the group consisting of R, D, E, H and Y;
- —X(302)—is selected from the group consisting of V and I;
- —X(303)—is selected from the group consisting of V, D, E and Y;
- —X(304)—is selected from the group consisting of S, D, H, L, N and T;
- —X(305)—is selected from the group consisting of V, E, T and Y;
- —X(313)—is selected from the group consisting of W and F;
- —X(317)—is selected from the group consisting of K, E and Q;
- —X(318)—is selected from the group consisting of E, H, L, Q, R and Y;
- —X(320)—is selected from the group consisting of K, D, F, G, H, I, L, N, P, S, T, V, W and Y;
- —X(322)—is selected from the group consisting of K, D, F, G, H, I, P, S, T, V, W and Y;
- —X(323)—is selected from the group consisting of V and I;
- —X(324)—is selected from the group consisting of S, D, F, G, H, I, L, M, P, R, T, V, W and Y;
- —X(325)—is 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;
- —X(326)—is selected from the group consisting of K, I, L, P and T;
- —X(327)—is selected from the group consisting of A, G, D, E, F, H, I, K, L, M, N, P, R, T, V, W and Y;
- —X(328)—is 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;
- —X(329)—is 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;
- —X(330)—is selected from the group consisting of A, E, F, G, H, I, L, M, N, P, R, T, V, W and Y;
- —X(331)—is selected from the group consisting of P, D, F, H, I, L, M, Q, R, T, V, W and Y;
- —X(332)—is selected from the group consisting of I, A, D, E, F, H, K, L, M, N, P, Q, R, S, T, V, W and Y;
- —X(333)—is selected from the group consisting of E, F, H, I, L, M, P, T and Y;
- —X(334)—is selected from the group consisting of K, F, I, P and T;
- —X(335)—is selected from the group consisting of T, D, F, G, H, I, L, M, N, P, R, S, V, W and Y;
- —X(336)—is selected from the group consisting of I, E, K and Y;
- —X(337)—is selected from the group consisting of S, E, H and N, and
- wherein the variant differs from SEQ ID NO:15 by at least one amino acid.
98 more elements
An IgG2 variant comprising an amino acid sequence having the formula:
- ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT
- VPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCC-X(221)-V-E-C-X(227)-PCPAPELLGGP-X(239)-
- X(240)-FLFPP-X(246)-PKDTLMIS-X(255)-TP-X(258)-V-X(260)-CVV-X(264)-DV-X(267)-X(268)-ED-
- X(271)-X(272)-V-X(274)-FNW-X(278)-VD-X(281)-V-X(283)-X(284)-HNAKT-X(290)-PR-X(293)-E-X(295)-
- FNSTFRVV-X(304)-VLTVVHQDWLNGKEYKCKV-X(324)-N-X(326)-X(327)-X(328)-P-X(330)-P-X(332)-
- X(333)-X(334)-
- TISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGS
- FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
- wherein
- —X(221)—is selected from the group consisting of no amino acid and K;
- —X(227)—is selected from the group consisting of P and G;
- —X(237)—is selected from the group consisting of G and D;
- —X(239)—is selected from the group consisting of S, D, E, N, Q and T;
- —X(240)—is selected from the group consisting of V, I and M;
- —X(246)—is selected from the group consisting of K, H and Y;
- —X(255)—is selected from the group consisting of R and Y;
- —X(258)—is selected from the group consisting of E, H and Y;
- —X(260)—is selected from the group consisting of T and H;
- —X(264)—is selected from the group consisting of V, I, T and Y;
- —X(267)—is selected from the group consisting of S, D and E;
- —X(268)—is selected from the group consisting of H, D and E;
- —X(271)—is selected from the group consisting of P and G;
- —X(272)—is selected from the group consisting of E, Y, H, R and I;
- —X(274)—is selected from the group consisting of Q and E;
- —X(278)—is selected from the group consisting of Y and T;
- —X(281)—is selected from the group consisting of G, D and E;
- —X(283)—is selected from the group consisting of E, L and H;
- —X(284)—is selected from the group consisting of V, E and D;
- —X(290)—is selected from the group consisting of K and N;
- —X(293)—is selected from the group consisting of E and R;
- —X(295)—is selected from the group consisting of Q and E;
- —X(304)—is selected from the group consisting of S and T;
- —X(324)—is selected from the group consisting of S, G and I;
- —X(326)—is selected from the group consisting of K and T;
- —X(327)—is selected from the group consisting of A, G and D;
- —X(328)—is selected from the group consisting of L, A, F, I and T;
- —X(330)—is selected from the group consisting of A, L, Y and I;
- —X(332)—is selected from the group consisting of I, D, E, N, Q and T;
- —X(333)—is selected from the group consisting of E and Y;
- —X(334)—is selected from the group consisting of K, F, I and T;
- and wherein at least one of the positions is different from the sequence of SEQ ID NO:15.
38 more elements
Dependencies are inferred from the claim text.