Anti-tissue factor antibodies with enhanced anticoagulant potency
AssigneeGenentech, Inc.
InventorsDaniel K. Kirchhofer, David G. Lowe, Leonard G. Presta
Life of this patent
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Abstract
The invention concerns anti-tissue factor (anti-TF) antibodies with enhanced anticoagulant potency, and methods and means for identifying, producing and using such antibodies. The anti-TF antibodies of the present invention are designed to comprise a region binding to an epitope in the C-terminal macromolecular substrate binding region of TF.
Claims43
A method for identifying anti-tissue factor (anti-TF) antibodies with enhanced anticoagulant potency, comprising (a) subjecting a plurality of anti-TF antibodies to epitope mapping, and (b) selecting from said plurality, antibodies binding to an epitope comprising at least part of the C-terminal macromolecular substrate-binding region of tissue factor (TF).
An anti-tissue factor (anti-TF) antibody heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 1 or SEQ ID NO:
- 2.
An anti-tissue factor (anti-TF) light chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 3 or SEQ ID NO:
- 4.
An anti-tissue factor (anti-TF) heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 5.
An anti-tissue factor (anti-TF) light chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 6.
An isolated nucleic acid comprising a sequence encoding an anti-TF antibody heavy chain variable domain of SEQ ID:
- 1, 2, or 5.
An isolated nucleic acid comprising a sequence encoding an anti-TF antibody light chain variable domain of SEQ ID NO:
- 3, 4, or 6.
A humanized anti-tissue factor (anti-TF) antibody comprising a heavy and a light chain variable domain, wherein said heavy chain variable domain comprises hypervariable regions CDR-H1 having the sequence of GFNIKEYYMH (SEQ ID NO:
- 7), CDR-H2 having the sequence of LIDPEQGNTIYDPKFQD (SEQ ID NO:
- 8) and CDR-H3 having the sequence of DTAAYFDY (SEQ ID NO:
- 9).
An antibody selected from the group consisting of (a) murine antibody D3 (D3Mur), (b) humanized antibody D3H44, (c) murine antibody 5G6, and (d) an antibody comprises essentially the same hypervariable regions as any one of antibodies of (a)-(c).
An isolated nucleic acid molecule comprising a sequence encoding a humanized antibody heavy chain variable domain comprising hypervariable regions CDR-H1 having the sequence of GFNIKEYYMH (SEQ ID NO:
- 7), CDR-H2 having the sequence of LIDPEQGNTIYDPKFQD (SEQ ID NO:
- 8) and CDR-H3 having the sequence of DTAAYFDY (SEQ ID NO:
- 9), or humanized antibody light chain variable domain comprising hypervariable regions CDR-L1 having the sequence of RASRDIKSYLN (SEQ ID NO:
- 10), CDR-L2 having the sequence of YATSLAE (SEQ ID NO:
- 11) and CDR-L3 having the sequence of LQHGESPWT (SEQ ID NO:
- 12).
A composition comprising an antibody selected from the group consisting of (a) murine antibody D3 (D3Mur), (b) humanized antibody D3H44, (c) murine antibody 5G6, and (d) an antibody comprising essentially the same hypervariable regions as any one of antibodies (a)-(c), in admixture with a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.