Novel heterodimeric proteins
AssigneeXencor, Inc.
InventorsJohn R. Desjarlais, Gregory L. Moore, Rumana Rashid, Matthew J. Bernett
Life of this patent
Estimating the term…
Abstract
The invention provides novel heterodimeric proteins including heterodimeric antibodies.
Claims49
(canceled)
A composition comprising an anti-CD3 variable region having a sequence comprising a vhCDR1 having the sequence T-Y-A-M-Xaa1, wherein Xaa1 is N, S or H (SEQ ID NO:435), a vhCDR2 having the sequence R-I-R-S-K-Xaa1-N-Xaa2-Y-A-T-Xaa3-Y-Y-A-Xaa4-S-V-K-G, wherein Xaa1 is Y or A, Xaa2 is N or S, Xaa3 is Y or A and Xaa4 is D or A (SEQ ID NO:436), a vhCDR3 having the sequence H-G-N-F-G-Xaa1-S-Y-V-S-W-F-Xaa2-Y, wherein Xaa1 is N, D or Q and Xaa2 is A or D (SEQ ID NO:437), a vlCDR1 having the sequence Xaa1-S-S-T-G-A-V-T-Xaa2-Xaa3-Xaa4-Y-A-N, wherein Xaa1 is G, R or K, Xaa2 is T or S, Xaa3 is S or G and Xaa4 is N or H, (SEQ ID NO:438), a vlCDR2 having the sequence Xaa1-T-N-Xaa2-R-A-Xaa3, wherein Xaa1 is G or D, Xaa2 is K or N, and Xaa3 is P or S (SEQ ID NO:439) and a vlCDR3 having the sequence Xaa1-L-W-Y-S-N-Xaa2-W-V, wherein Xaa1 is A or L and Xaa2 is L or H (SEQ ID NO:440).
3-4. (canceled)
7-13. (canceled)
15-17. (canceled)
(canceled)
A heterodimeric antibody comprising:
- a) a first heavy chain comprising:
- i) a first Fc domain;
- and
- ii) a single chain Fv region (scFv) that binds CD3 comprising aa vhCDR1 having the sequence T-Y-A-M-Xaa1, wherein Xaa1 is N, S or H (SEQ ID NO:435), a vhCDR2 having the sequence R-I-R-S-K-Xaa1-N-Xaa2-Y-A-T-Xaa3-Y-Y-A-Xaa4-S-V-K-G, wherein Xaa1 is Y or A, Xaa2 is N or S, Xaa3 is Y or A and Xaa4 is D or A (SEQ ID NO:436), a vhCDR3 having the sequence H-G-N-F-G-Xaa1-S-Y-V-S-W-F-Xaa2-Y, wherein Xaa1 is N, D or Q and Xaa2 is A or D (SEQ ID NO:437), a vlCDR1 having the sequence Xaa1-S-S-T-G-A-V-T-Xaa2-Xaa3-Xaa4-Y-A-N, wherein Xaa1 is G, R or K, Xaa2 is T or S, Xaa3 is S or G and Xaa4 is N or H, (SEQ ID NO:438), a vlCDR2 having the sequence Xaa1-T-N-Xaa2-R-A-Xaa3, wherein Xaa1 is G or D, Xaa2 is K or N, and Xaa3 is P or S (SEQ ID NO:439) and a vlCDR3 having the sequence Xaa1-L-W-Y-S-N-Xaa2-W-V, wherein Xaa1 is A or L and Xaa2 is L or H (SEQ ID NO:440);
- and
- b) a second heavy chain comprising:
- i) a second Fc domain;
- and
- ii) a first variable heavy chain;
- and
- c) a light chain;
- wherein said first and second Fc domains are different.
23-26. (canceled)
(canceled)
30-33. (canceled)
35-38. (canceled)
A heterodimeric antibody comprising:
- a) a first heavy chain comprising:
- i) a first Fc domain;
- and
- ii) a single chain Fv region (scFv) that binds a first antigen;
- wherein said scFv comprises a charged scFv linker;
- and
- b) a second heavy chain comprising:
- i) a second Fc domain;
- ii) a first variable heavy chain;
- and
- c) a light chain.
43-44. (canceled)
A heterodimeric antibody comprising:
- a) a first heavy chain comprising:
- i) a first Fc domain;
- and
- ii) a single chain Fv region (scFv) that binds a first antigen;
- and
- b) a second heavy chain comprising:
- i) a second Fc domain;
- and
- ii) a first variable heavy chain;
- and
- c) a light chain;
- wherein said first and second Fc domains comprise a variant set selected from the variants listed in FIG. 9.
51-52. (canceled)
55-56. (canceled)
A host cell comprising the nucleic acid composition of 57.
A heterodimeric antibody comprising:
- a) a first heavy chain comprising:
- i) a first Fc domain;
- and
- ii) a single chain Fv region (scFv) that binds a first antigen;
- and
- b) a second heavy chain comprising:
- i) a second Fe domain;
- and
- ii) a first variable heavy chain;
- and
- c) a light chain;
- wherein one of said first and second Fc domains comprises an Fcγ receptor ablation variant set.
62-66. (canceled)
A heterodimeric antibody comprising:
- a) a first heavy chain comprising:
- i) a first Fc domain;
- and
- ii) a single chain Fv region that binds a first antigen;
- and
- b) a second heavy chain comprising:
- i) a second Fc domain;
- and
- ii) a first variable heavy chain;
- and
- c) a light chain;
- wherein said first and second Fc domains comprise a set of variants as shown in FIG. 9, 32 or 33.
A heterodimeric antibody comprising:
- a) a first heavy chain comprising:
- i) a first Fc domain;
- and
- ii) a first single chain Fv region (scFv) that binds a first antigen;
- wherein said first scFv comprises a first charged scFv linker;
- and
- b) a second heavy chain comprising:
- i) a second Fc domain;
- ii) a second scFv that binds a second antigen.
73-80. (canceled)
A method of making a heterodimeric antibody comprising:
- a) providing a first nucleic acid encoding a first heavy chain comprising:
- i) a first heavy chain comprising:
- 1 a first Fc domain;
- and
- 2 a single chain Fv region (scFv) that binds a first antigen;
- wherein said scFv comprises a charged linker;
- and
- b) providing a second nucleic acid encoding a second heavy chain comprising:
- i) a second Fc domain;
- ii) a first variable heavy chain;
- and
- c) providing a third nucleic acid comprising a light chain;
- d) expressing said first, second and third nucleic acids in a host cell to produce a first, second and third amino acid sequence, respectively;
- e) loading said first, second and third amino acid sequences onto an ion exchange column;
- and
- f) collecting the heterodimeric fraction.
Dependencies are inferred from the claim text.