Oregon Health & Science University

Vanderbilt University

Aronora Inc.

Saint Louis University

Absci LLC

The Scripps Research Institute

Tucker, Erik I.

Gruber, Andras

Gailani, David

Andras Gruber

John H Griffin

Erik Tucker

David Gailani

Stephen R Hanson

Sean McClain

Mark Valasek

Philberta Y Leung

Nicola Pozzi

Enrico Di Cera

David Collier Wood

Anton Matafonov

Prafull Gandhi

Leslie Pelc

Michael Wallisch

Christina U Lorentz

Erik Ian Tucker

Stephen Raymond Hanson

Erik I Tucker

Owen JT Mccarty

Monoclonal antibodies that bind, such as specifically bind, blood protein factor XII (FXII) are described. The monoclonal antibodies (including antigen-binding fragments thereof) are capable of forming immune complexes with human FXII and inhibiting FXII activity, resulting in safe anti-inflammatory and anti-thrombotic effects.

Therapeutic factor XII antibody

Compositions and methods for inhibiting thrombosis without compromising hemostasis are described. Compositions include anti-factor XI monoclonal antibodies (aXIMabs) capable of binding to an epitope on the heavy chain of human FXI, particularly the A3 domain of the heavy chain of human FXI. Compositions also include epitope-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The disclosure further includes pharmaceutical compositions comprising the disclosed anti-factor XI monoclonal antibodies, or epitope-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier. Methods of the disclosure include administering the compositions described above to a subject in need thereof for the purpose of inhibiting thrombosis, reducing a required dose of an antithrombotic agent in the treatment of thrombosis, treating metastatic cancer, or treating an acute inflammatory reaction.

Anti-factor XI monoclonal antibodies and methods of use thereof

The present invention provides methods of producing thrombin using coordinated coexpression systems, and particularly inducible coexpression systems, capable of controlled induction of expression of each gene product required for the production of thrombin, and the thrombin produced by this method.

Coordinated coexpression of thrombin

Disclosed herein are monoclonal antibodies specific for factor XI (fXI) that prevent activation of fXI by factor XIIa (fXIIa). The monoclonal antibodies are universal fXI antibodies, capable of binding all mammalian species tested. The anti-fXI monoclonal antibodies prolong clotting time in mammalian plasmas. Moreover, administration of the fXI monoclonal antibodies disclosed herein results in inhibition of thrombosis without altering hemostasis in animal models of thrombosis. Thus, provided herein are monoclonal antibodies specific for fXI that block activation of fXI by fXIIa, compositions and immunoconjugates comprising such antibodies and their methods of use.

Anti-fXI antibodies and methods of use

Provided are antibodies that selectively bind to and inhibit activation of coagulation factor XII. Methods of treatment employing these antibodies are described herein.

Antibodies against factor XII and uses thereof

The present invention relates to compositions and methods for inhibiting thrombosis without compromising hemostasis. Compositions include anti-factor XI monoclonal antibodies (aXIMabs) capable of binding to an epitope on the heavy chain of human FXI, particularly the A3 domain of the heavy chain of human FXI. Compositions also include epitope-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The invention further includes pharmaceutical compositions comprising the anti-factor XI monoclonal antibodies of the invention, or epitope-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier. Methods of the invention comprise administering the compositions described above to a subject in need thereof for the purpose of inhibiting thrombosis, reducing a required dose of an antithrombotic agent in the treatment of thrombosis, treating metastatic cancer, or treating an acute inflammatory reaction.

One aspect of the invention contemplates a mutant E-WE thrombin precursor that contains the SEQ ID NO:1 amino acid residue sequence. Another aspect contemplates a thrombin precursor that contains the amino acid residue sequence Asp/Glu-Gly-Arg at positions 325, 326 and 327 based on the preprothrombin sequence. A third aspect contemplates a thrombin precursor that contains the SEQ ID NO:1 amino acid residue sequence as well as the amino acid residue sequence Asp/Glu Gly Arg at positions 325, 326 and 327 based on the preprothrombin sequence. Also contemplated is a composition that contains an effective amount of mutant thrombin dissolved or dispersed in a pharmaceutically acceptable carrier. A method is also disclosed for enhancing treating and preventing thrombosis in a mammal in need using that composition.

Expression of thrombin variants

Polynucleotides encoding anti-factor XI monoclonal antibodies and methods of use thereof

The present invention relates to compositions and methods for inhibiting thrombosis without compromising hemostasis. Compositions include anti-factor XI monoclonal antibodies (aXIMabs) capable of binding to an epitope on the heavy chain of human FXI, particularly the A3 domain of the heavy chain of human FXI. Compositions also include epitope-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The invention further includes pharmaceutical compositions comprising the anti-factor XI monoclonal antibodies of the invention, or epitope-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier. Methods of the invention comprise administering the compositions described above to a subject in need thereof for the purpose of inhibiting thrombosis, reducing a required dose of an antithrombotic agent in the treatment of thrombosis, treating metastatic cancer, or treating an acute inflammatory reaction. Methods for making an anti-factor XI monoclonal antibody, or epitope-binding fragments, variants, or derivatives thereof, are also provided.

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Portland, OR, United States of America

Andras Gruber